Let-7 microRNA family

let-7 microRNA precursor
Predicted secondary structure and sequence conservation of let-7
Identifiers
Symbol	let-7
Rfam	RF00027
miRBase	MI0000001
miRBase family	MIPF0000002
Other data
RNA type	Gene; miRNA
Domain(s)	Eukaryota
GO	GO:0035195 GO:0035068
SO	SO:0001244
PDB structures	PDBe

The Let-7 microRNA precursor gives rise to let-7, a microRNA (miRNA) involved in control of stem-cell division and differentiation.[1] let-7, short for "lethal-7", was discovered along with the miRNA lin-4 in a study of developmental timing in C. elegans,[2] making these miRNAs the first ever discovered. let-7 was later identified in humans as the first human miRNA , and is highly conserved across many species.[3][4] Dysregulation of let-7 contributes to cancer development in humans by preventing differentiation of cells, leaving them stuck in a stem-cell like state.[1] let-7 is therefore classified as a tumor suppressor.

The let-7 microRNA family refers to the many slight variations of let-7 that exist both within a single organism and across species. In humans, for example, there are ten unique let-7 family member sequences: let-7a through g, let-7i, mir-98, and mir-202.[1]

In humans, mature let-7 acts via RNA-induced silencing by complexing with RISC and binding to target mRNA, preventing translation into protein. Known targets of let-7 include proteins related to the cell cycle and proliferation, such as MYC, RAS, cyclin D, HMGA2, and CDC25A.[1] Knockdown of these proteins by let-7 prevents proliferation and induces differentiation of cells. Important inhibitors of let-7 include LIN28, which binds to let-7 directly,[5] and the proto-oncogene MYC, which suppresses expression.[6]

Genomic Locations

In human genome, the cluster let-7a-1/let-7f-1/let-7d is inside the region B at 9q22.3, with the defining marker D9S280-D9S1809. One minimal LOH (loss of heterozygosity) region, between loci D11S1345-D11S1316, contains the cluster miR-125b1/let-7a-2/miR-100. The cluster miR-99a/let-7c/miR-125b-2 is in a 21p11.1 region of HD (homozygous deletions). The cluster let-7g/miR-135-1 is in region 3 at 3p21.1-p21.2.[7]

The let-7 family

The lethal-7 (let-7) gene was first discovered in the nematode C. elegans as a key developmental regulator and became one of the first two known microRNAs (the other one is lin-4).[8] Soon, let-7 was found in the fruit fly (Drosophila), and identified as the first known human miRNA by a BLAST (basic local alignment search tool) research.[9] The mature form of let-7 family members is highly conserved across species.

In C. elegans

In C. elegans, the let-7 family consists of genes encoding nine miRNAs sharing the same seed sequence.[10] Among them, let-7, mir-84, mir-48 and mir-241 are involved in the C. elegans heterochronic pathway, sequentially controlling developmental timing of larva transitions.[11] Most animals with loss-of-function let-7 mutation burst through their vulvas and die, and therefore the mutant is lethal (let).[8] The mutants of other let-7 family members have a radio-resistant phenotype in vulval cells, which may be related to their ability to repress RAS.[12]

In Drosophila

There is only one single let-7 gene in the Drosophila genome, which has the identical mature sequence to the one in C. elegans.[13] The role of let-7 has been demonstrated in regulating the timing of neuromuscular junction formation in the abdomen and cell-cycle in the wing.[14] Furthermore, the expression of pri-, pre- and mature let-7 have the same rhythmic pattern with the hormone pulse before each cuticular molt in Drosophila.[15]

In vertebrates

The let-7 family has a lot more members in vertebrates than in C. elegans and Drosophila.[13] The sequences, expression timing, as well as genomic clustering of these miRNAs members are all conserved across species.[16] The direct role of let-7 family in vertebrate development has not been clearly shown as in less complex organisms, yet the expression pattern of let-7 family is indeed temporally regulated during developmental processes.[17] Functionally, let-7 has been shown in early vertebrates to control the differentiation of mesoderm and ectoderm.[18] Given that the expression levels of let-7 members are significantly low in human cancers and cancer stem cells,[19] the major function of let-7 genes may be to promote terminal differentiation in development and tumor suppression.

Regulation of expression

Although the levels of mature let-7 members are undetectable in undifferentiated cells, the primary transcripts and the hairpin precursors of let-7 are present in these cells.[20] It indicates that the mature let-7 miRNAs may be regulated in a post-transcriptional manner.

By pluripotency promoting factor LIN28

As one of the genes involved in (but not essential for) induced pluripotent stem (iPS) cell reprogramming,[21] LIN28 expression is reciprocal to that of mature let-7.[5] LIN28 selectively binds the primary and precursor forms of let-7, and inhibits the processing of pri-let-7 to form the hairpin precursor.[22] This binding is facilitated by the conserved loop sequence of primary let-7 family members and RNA-binding domains of LIN28 proteins.[23] Lin-28 uses two zinc knuckle domains to recognize the NGNNG motif in the let-7 precursors,[24] while the Cold-shock domain, connected by a flexible linker, binds to a closed loop in the precursors.[25] On the other hand, let-7 miRNAs in mammals have been shown to regulate LIN28,[26] which implies that let-7 might enhance its own level by repressing LIN28, its negative regulator.[27]

In autoregulatory loop with MYC

Expression of let-7 members is controlled by MYC binding to their promoters. The levels of let-7 have been reported to decrease in models of MYC-mediated tumorigenesis, and to increase when MYC is inhibited by chemicals.[6] In a twist, there are let-7-binding sites in MYC 3' untranslated region(UTR) according to bioinformatic analysis, and let-7 overexpression in cell culture decreased MYC mRNA levels.[28] Therefore, there is a double-negative feedback loop between MYC and let-7. Furthermore, let-7 could lead to IMP1 (insulin-like growth factor II mRNA-binding protein) depletion, which destabilizes MYC mRNA, thus forming an indirect regulatory pathway.[29]

Targets of let-7

Oncogenes: RAS, HMGA2

Let-7 has been demonstrated to be a direct regulator of RAS expression in human cells[30] All the three RAS genes in human, K-, N-, and H-, have the predicted let-7 binding sequences in their 3'UTRs. In lung cancer patient samples, expression of RAS and let-7 showed reciprocal pattern, which has low let-7 and high RAS in cancerous cells, and high let-7 and low RAS in normal cells. Another oncogene, high mobility group A2 (HMGA2), has also been identified as a target of let-7. Let-7 directly inhibits HMGA2 by binding to its 3'UTR.[31] Removal of let-7 binding site by 3'UTR deletion cause overexpression of HMGA2 and formation of tumor.

Cell cycle, proliferation, and apoptosis regulators

Microarray analyses revealed many genes regulating cell cycle and cell proliferation that are responsive to alteration of let-7 levels, including cyclin A2, CDC34, Aurora A and B kinases (STK6 and STK12), E2F5, and CDK8, among others.[30] Subsequent experiments confirmed the direct effects of some of these genes, such as CDC25A and CDK6.[32] Let-7 also inhibits several components of DNA replication machinery, transcription factors, even some tumor suppressor genes and checkpoint regulators.[30] Apoptosis is regulated by let-7 as well, through Casp3, Bcl2, Map3k1 and Cdk5 modulation.[33]

Immunity

Let-7 has been implicated in post-transcriptional control of innate immune responses to pathogenic agents. Macrophages stimulated with live bacteria or purified microbial components down-regulate the expression of several members of the let-7 microRNA family to relieve repression of immune-modulatory cytokines IL-6 and IL-10.[34][35] Let-7 has also been implicated in the negative regulation of TLR4, the major immune receptor of microbial lipopolysaccharide and down-regulation of let-7 both upon microbial and protozoan infection might elevate TLR4 signaling and expression.[36][37] Let-7 has furthermore been reported to regulate the production of cytokine IL-13 by T lymphocytes during allergic airway inflammation thus linking this microRNA to adaptive immunity as well.[38] Down-modulation of let-7 negative regulator Lin28b in human T lymphocytes is believed to accrue during early neonate development to reprogram the immune system towards defense.[39]

Potential clinical use in cancer

Given the prominent phenotype of cell overproliferation and dedifferentiation by let-7 loss-of-function in nematodes, and the role of its targets on cell destiny determination, let-7 is closely associated with human cancer and acts as a tumor suppressor.

Prognostic Biomarkers

Numerous reports have shown that the expression levels of let-7 are frequently low and the chromosomal clusters of let-7 are often deleted in many cancers.[7] Let-7 is expressed at higher levels in more differentiated tumors, which also have lower levels of activated oncogenes such as RAS and HMGA2. Therefore, expression levels of let-7 could be prognostic markers in several cancers associated with differentiation stages.[40] In lung cancer, for example, reduced expression of let-7 is significantly correlated with reduced postoperative survival.[41] The expression of let-7b and let-7g microRNAs are significantly associated with overall survival in 1262 breast cancer patients.[42]

Therapy

Let-7 is also a very attractive potential therapeutic that can prevent tumorigenesis and angiogenesis, typically in cancers that underexpress let-7.[43] Lung cancer, for instance, has several key oncogenic mutations including p53, RAS and MYC, some of which may directly correlate with the reduced expression of let-7, and may be repressed by introduction of let-7.[41] Intranasal administration of let-7 has already been found effective in reducing tumor growth in a transgenic mouse model of lung cancer.[44] Similar restoration of let-7 was also shown to inhibit cell proliferation in breast, colon and hepatic cancers, lymphoma, and uterine leiomyoma.[45]

References

1. Roush, Sarah; Slack, Frank J. (2008). "The let-7 family of microRNAs". Trends in Cell Biology. 18 (10): 505–516. doi:10.1016/j.tcb.2008.07.007.
2. Rougvie AE (September 2001). "Control of developmental timing in animals". Nature Reviews. Genetics. 2 (9): 690–701. doi:10.1038/35088566. PMID 11533718. S2CID 44335211.
3. Pasquinelli, Amy E.; Reinhart, Brenda J.; Slack, Frank; Martindale, Mark Q.; Kuroda, Mitzi I.; Maller, Betsy; Hayward, David C.; Ball, Eldon E.; Degnan, Bernard; Müller, Peter; Spring, Jürg; Srinivasan, Ashok; Fishman, Mark; Finnerty, John; Corbo, Joseph (2000). "Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA". Nature. 408 (6808): 86–89. doi:10.1038/35040556. ISSN 1476-4687.
4. Pasquinelli, Amy E.; McCoy, Adam; Jiménez, Eva; Saló, Emili; Ruvkun, Gary; Martindale, Mark Q.; Baguñà, Jaume (2003). "Expression of the 22 nucleotide let‐7 heterochronic RNA throughout the Metazoa: a role in life history evolution?". Evolution & Development. 5 (4): 372–378. doi:10.1046/j.1525-142X.2003.03044.x. ISSN 1520-541X.
5. Viswanathan SR, Daley GQ, Gregory RI (April 2008). "Selective blockade of microRNA processing by Lin28". Science. 320 (5872): 97–100. Bibcode:2008Sci...320...97V. doi:10.1126/science.1154040. PMC 3368499. PMID 18292307.
6. Chang TC, Yu D, Lee YS, Wentzel EA, Arking DE, West KM, et al. (January 2008). "Widespread microRNA repression by Myc contributes to tumorigenesis". Nature Genetics. 40 (1): 43–50. doi:10.1038/ng.2007.30. PMC 2628762. PMID 18066065.
7. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. (March 2004). "Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers". Proceedings of the National Academy of Sciences of the United States of America. 101 (9): 2999–3004. Bibcode:2004PNAS..101.2999C. doi:10.1073/pnas.0307323101. PMC 365734. PMID 14973191.
8. Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, et al. (February 2000). "The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans". Nature. 403 (6772): 901–906. Bibcode:2000Natur.403..901R. doi:10.1038/35002607. PMID 10706289. S2CID 4384503.
9. Pasquinelli AE, Reinhart BJ, Slack F, Martindale MQ, Kuroda MI, Maller B, et al. (November 2000). "Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA". Nature. 408 (6808): 86–89. Bibcode:2000Natur.408...86P. doi:10.1038/35040556. PMID 11081512. S2CID 4401732.
10. Lim LP, Lau NC, Weinstein EG, Abdelhakim A, Yekta S, Rhoades MW, et al. (April 2003). "The microRNAs of Caenorhabditis elegans". Genes & Development. 17 (8): 991–1008. doi:10.1101/gad.1074403. PMC 196042. PMID 12672692.
11. Moss EG (June 2007). "Heterochronic genes and the nature of developmental time". Current Biology. 17 (11): R425 – R434. Bibcode:2007CBio...17.R425M. doi:10.1016/j.cub.2007.03.043. PMID 17550772.
12. Weidhaas JB, Babar I, Nallur SM, Trang P, Roush S, Boehm M, et al. (December 2007). "MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy". Cancer Research. 67 (23): 11111–11116. doi:10.1158/0008-5472.CAN-07-2858. PMC 6070379. PMID 18056433.
13. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T (October 2001). "Identification of novel genes coding for small expressed RNAs". Science. 294 (5543): 853–858. Bibcode:2001Sci...294..853L. doi:10.1126/science.1064921. hdl:11858/00-001M-0000-0012-F65F-2. PMID 11679670. S2CID 18101169.
14. Caygill EE, Johnston LA (July 2008). "Temporal regulation of metamorphic processes in Drosophila by the let-7 and miR-125 heterochronic microRNAs". Current Biology. 18 (13): 943–950. Bibcode:2008CBio...18..943C. doi:10.1016/j.cub.2008.06.020. PMC 2736146. PMID 18571409.
15. Thummel CS (October 2001). "Molecular mechanisms of developmental timing in C. elegans and Drosophila". Developmental Cell. 1 (4): 453–465. doi:10.1016/S1534-5807(01)00060-0. PMID 11703937.
16. Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A (October 2004). "Identification of mammalian microRNA host genes and transcription units". Genome Research. 14 (10A): 1902–1910. doi:10.1101/gr.2722704. PMC 524413. PMID 15364901.
17. Kloosterman WP, Plasterk RH (October 2006). "The diverse functions of microRNAs in animal development and disease". Developmental Cell. 11 (4): 441–450. doi:10.1016/j.devcel.2006.09.009. PMID 17011485.
18. Colas AR, McKeithan WL, Cunningham TJ, Bushway PJ, Garmire LX, Duester G, et al. (December 2012). "Whole-genome microRNA screening identifies let-7 and mir-18 as regulators of germ layer formation during early embryogenesis". Genes & Development. 26 (23): 2567–2579. doi:10.1101/gad.200758.112. PMC 3521625. PMID 23152446.
19. Esquela-Kerscher A, Slack FJ (April 2006). "Oncomirs - microRNAs with a role in cancer". Nature Reviews. Cancer. 6 (4): 259–269. doi:10.1038/nrc1840. PMID 16557279. S2CID 10620165.
20. Thomson JM, Newman M, Parker JS, Morin-Kensicki EM, Wright T, Hammond SM (August 2006). "Extensive post-transcriptional regulation of microRNAs and its implications for cancer". Genes & Development. 20 (16): 2202–2207. doi:10.1101/gad.1444406. PMC 1553203. PMID 16882971.
21. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, et al. (December 2007). "Induced pluripotent stem cell lines derived from human somatic cells". Science. 318 (5858): 1917–1920. Bibcode:2007Sci...318.1917Y. doi:10.1126/science.1151526. PMID 18029452. S2CID 86129154.
22. Newman MA, Thomson JM, Hammond SM (August 2008). "Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing". RNA. 14 (8): 1539–1549. doi:10.1261/rna.1155108. PMC 2491462. PMID 18566191.
23. Piskounova E, Viswanathan SR, Janas M, LaPierre RJ, Daley GQ, Sliz P, Gregory RI (August 2008). "Determinants of microRNA processing inhibition by the developmentally regulated RNA-binding protein Lin28". The Journal of Biological Chemistry. 283 (31): 21310–21314. doi:10.1074/jbc.C800108200. PMID 18550544.
24. Loughlin FE, Gebert LF, Towbin H, Brunschweiger A, Hall J, Allain FH (December 2011). "Structural basis of pre-let-7 miRNA recognition by the zinc knuckles of pluripotency factor Lin28". Nature Structural & Molecular Biology. 19 (1): 84–89. doi:10.1038/nsmb.2202. PMID 22157959. S2CID 2201304.
25. Nam Y, Chen C, Gregory RI, Chou JJ, Sliz P (November 2011). "Molecular basis for interaction of let-7 microRNAs with Lin28". Cell. 147 (5): 1080–1091. doi:10.1016/j.cell.2011.10.020. PMC 3277843. PMID 22078496.
26. Moss EG, Tang L (June 2003). "Conservation of the heterochronic regulator Lin-28, its developmental expression and microRNA complementary sites". Developmental Biology. 258 (2): 432–442. doi:10.1016/S0012-1606(03)00126-X. PMID 12798299.
27. Ali PS, Ghoshdastider U, Hoffmann J, Brutschy B, Filipek S (November 2012). "Recognition of the let-7g miRNA precursor by human Lin28B". FEBS Letters. 586 (22): 3986–3990. Bibcode:2012FEBSL.586.3986S. doi:10.1016/j.febslet.2012.09.034. PMID 23063642. S2CID 28899778.
28. Koscianska E, Baev V, Skreka K, Oikonomaki K, Rusinov V, Tabler M, Kalantidis K (September 2007). "Prediction and preliminary validation of oncogene regulation by miRNAs". BMC Molecular Biology. 8: 79. doi:10.1186/1471-2199-8-79. PMC 2096627. PMID 17877811.
29. Ioannidis P, Mahaira LG, Perez SA, Gritzapis AD, Sotiropoulou PA, Kavalakis GJ, et al. (May 2005). "CRD-BP/IMP1 expression characterizes cord blood CD34+ stem cells and affects c-myc and IGF-II expression in MCF-7 cancer cells". The Journal of Biological Chemistry. 280 (20): 20086–20093. doi:10.1074/jbc.M410036200. PMID 15769738.
30. Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, et al. (March 2005). "RAS is regulated by the let-7 microRNA family". Cell. 120 (5): 635–647. doi:10.1016/j.cell.2005.01.014. PMID 15766527.
31. Mayr C, Hemann MT, Bartel DP (March 2007). "Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation". Science. 315 (5818): 1576–1579. Bibcode:2007Sci...315.1576M. doi:10.1126/science.1137999. PMC 2556962. PMID 17322030.
32. Johnson CD, Esquela-Kerscher A, Stefani G, Byrom M, Kelnar K, Ovcharenko D, et al. (August 2007). "The let-7 microRNA represses cell proliferation pathways in human cells". Cancer Research. 67 (16): 7713–7722. doi:10.1158/0008-5472.CAN-07-1083. PMID 17699775.
33. He YJ, Guo L, D ZH. (2009) Let-7 and mir-24 in uvb-induced apoptosis [Chinese]. Zhonghua Fang She Yi Xue Yu Fang Hu Za Zhi. 29, 234–6.
34. Schulte LN, Eulalio A, Mollenkopf HJ, Reinhardt R, Vogel J (May 2011). "Analysis of the host microRNA response to Salmonella uncovers the control of major cytokines by the let-7 family". The EMBO Journal. 30 (10): 1977–1989. doi:10.1038/emboj.2011.94. PMC 3098495. PMID 21468030.
35. Liu Y, Chen Q, Song Y, Lai L, Wang J, Yu H, et al. (June 2011). "MicroRNA-98 negatively regulates IL-10 production and endotoxin tolerance in macrophages after LPS stimulation". FEBS Letters. 585 (12): 1963–1968. Bibcode:2011FEBSL.585.1963L. doi:10.1016/j.febslet.2011.05.029. PMID 21609717. S2CID 2416276.
36. Hu G, Zhou R, Liu J, Gong AY, Eischeid AN, Dittman JW, Chen XM (August 2009). "MicroRNA-98 and let-7 confer cholangiocyte expression of cytokine-inducible Src homology 2-containing protein in response to microbial challenge". Journal of Immunology. 183 (3): 1617–1624. doi:10.4049/jimmunol.0804362. PMC 2906382. PMID 19592657.
37. Androulidaki A, Iliopoulos D, Arranz A, Doxaki C, Schworer S, Zacharioudaki V, et al. (August 2009). "The kinase Akt1 controls macrophage response to lipopolysaccharide by regulating microRNAs". Immunity. 31 (2): 220–231. doi:10.1016/j.immuni.2009.06.024. PMC 2865583. PMID 19699171.
38. Kumar M, Ahmad T, Sharma A, Mabalirajan U, Kulshreshtha A, Agrawal A, Ghosh B (November 2011). "Let-7 microRNA-mediated regulation of IL-13 and allergic airway inflammation". The Journal of Allergy and Clinical Immunology. 128 (5): 1077–1085. doi:10.1016/j.jaci.2011.04.034. PMID 21616524.
39. Yuan J, Nguyen CK, Liu X, Kanellopoulou C, Muljo SA (March 2012). "Lin28b reprograms adult bone marrow hematopoietic progenitors to mediate fetal-like lymphopoiesis". Science. 335 (6073): 1195–1200. Bibcode:2012Sci...335.1195Y. doi:10.1126/science.1216557. PMC 3471381. PMID 22345399.
40. Shell S, Park SM, Radjabi AR, Schickel R, Kistner EO, Jewell DA, et al. (July 2007). "Let-7 expression defines two differentiation stages of cancer". Proceedings of the National Academy of Sciences of the United States of America. 104 (27): 11400–11405. Bibcode:2007PNAS..10411400S. doi:10.1073/pnas.0704372104. PMC 2040910. PMID 17600087.
41. Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, et al. (June 2004). "Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival". Cancer Research. 64 (11): 3753–3756. doi:10.1158/0008-5472.CAN-04-0637. PMID 15172979.
42. Lánczky A, Nagy Á, Bottai G, Munkácsy G, Szabó A, Santarpia L, Győrffy B (December 2016). "miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients". Breast Cancer Research and Treatment. 160 (3): 439–446. doi:10.1007/s10549-016-4013-7. PMID 27744485. S2CID 11165696.
43. Kuehbacher A, Urbich C, Zeiher AM, Dimmeler S (July 2007). "Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis". Circulation Research. 101 (1): 59–68. doi:10.1161/CIRCRESAHA.107.153916. PMID 17540974.
44. Esquela-Kerscher A, Trang P, Wiggins JF, Patrawala L, Cheng A, Ford L, et al. (March 2008). "The let-7 microRNA reduces tumor growth in mouse models of lung cancer". Cell Cycle. 7 (6): 759–764. doi:10.4161/cc.7.6.5834. PMID 18344688.
45. Barh D, Malhotra R, Ravi B, Sindhurani P (February 2010). "MicroRNA let-7: an emerging next-generation cancer therapeutic". Current Oncology. 17 (1): 70–80. doi:10.3747/co.v17i1.356. PMC 2826782. PMID 20179807.

Further reading

• Dangi-Garimella S, Strouch MJ, Grippo PJ, Bentrem DJ, Munshi HG (February 2011). "Collagen regulation of let-7 in pancreatic cancer involves TGF-β1-mediated membrane type 1-matrix metalloproteinase expression". Oncogene. 30 (8): 1002–1008. doi:10.1038/onc.2010.485. PMC 3172057. PMID 21057545.
• Yang X, Lin X, Zhong X, Kaur S, Li N, Liang S, et al. (November 2010). "Double-negative feedback loop between reprogramming factor LIN28 and microRNA let-7 regulates aldehyde dehydrogenase 1-positive cancer stem cells". Cancer Research. 70 (22): 9463–9472. doi:10.1158/0008-5472.CAN-10-2388. PMC 3057570. PMID 21045151.
• Ohshima K, Inoue K, Fujiwara A, Hatakeyama K, Kanto K, Watanabe Y, et al. (October 2010). Wölfl S (ed.). "Let-7 microRNA family is selectively secreted into the extracellular environment via exosomes in a metastatic gastric cancer cell line". PLOS ONE. 5 (10): e13247. Bibcode:2010PLoSO...513247O. doi:10.1371/journal.pone.0013247. PMC 2951912. PMID 20949044.
• Ramachandran R, Fausett BV, Goldman D (November 2010). "Ascl1a regulates Müller glia dedifferentiation and retinal regeneration through a Lin-28-dependent, let-7 microRNA signalling pathway". Nature Cell Biology. 12 (11): 1101–1107. doi:10.1038/ncb2115. PMC 2972404. PMID 20935637.
• Ruzzo A, Canestrari E, Galluccio N, Santini D, Vincenzi B, Tonini G, et al. (January 2011). "Role of KRAS let-7 LCS6 SNP in metastatic colorectal cancer patients". Annals of Oncology. 22 (1): 234–235. doi:10.1093/annonc/mdq472. PMID 20926546.
• Garbuzov A, Tatar M (2010). "Hormonal regulation of Drosophila microRNA let-7 and miR-125 that target innate immunity". Fly. 4 (4): 306–311. doi:10.4161/fly.4.4.13008. PMC 3174482. PMID 20798594.
• Ji J, Wang XW (November 2010). "A Yin-Yang balancing act of the lin28/let-7 link in tumorigenesis". Journal of Hepatology. 53 (5): 974–975. doi:10.1016/j.jhep.2010.07.001. PMC 2949515. PMID 20739081.
• Osada H, Takahashi T (January 2011). "let-7 and miR-17-92: small-sized major players in lung cancer development". Cancer Science. 102 (1): 9–17. doi:10.1111/j.1349-7006.2010.01707.x. PMID 20735434.
• He Y, Yang C, Kirkmire CM, Wang ZJ (July 2010). "Regulation of opioid tolerance by let-7 family microRNA targeting the mu opioid receptor". The Journal of Neuroscience. 30 (30): 10251–10258. doi:10.1523/JNEUROSCI.2419-10.2010. PMC 2943348. PMID 20668208.
• Cevec M, Thibaudeau C, Plavec J (November 2010). "NMR structure of the let-7 miRNA interacting with the site LCS1 of lin-41 mRNA from Caenorhabditis elegans". Nucleic Acids Research. 38 (21): 7814–7821. doi:10.1093/nar/gkq640. PMC 2995062. PMID 20660479.
• Nie K, Zhang T, Allawi H, Gomez M, Liu Y, Chadburn A, et al. (September 2010). "Epigenetic down-regulation of the tumor suppressor gene PRDM1/Blimp-1 in diffuse large B cell lymphomas: a potential role of the microRNA let-7". The American Journal of Pathology. 177 (3): 1470–1479. doi:10.2353/ajpath.2010.091291. PMC 2928978. PMID 20651244.
• Polikepahad S, Knight JM, Naghavi AO, Oplt T, Creighton CJ, Shaw C, et al. (September 2010). "Proinflammatory role for let-7 microRNAS in experimental asthma". The Journal of Biological Chemistry. 285 (39): 30139–30149. doi:10.1074/jbc.M110.145698. PMC 2943272. PMID 20630862.
• Newman MA, Hammond SM (August 2010). "Lin-28: an early embryonic sentinel that blocks Let-7 biogenesis". The International Journal of Biochemistry & Cell Biology. 42 (8): 1330–1333. doi:10.1016/j.biocel.2009.02.023. PMID 20619222.
• Lee ST, Chu K, Oh HJ, Im WS, Lim JY, Kim SK, et al. (March 2011). "Let-7 microRNA inhibits the proliferation of human glioblastoma cells". Journal of Neuro-Oncology. 102 (1): 19–24. doi:10.1007/s11060-010-0286-6. PMID 20607356. S2CID 29835621.
• Zhang W, Winder T, Ning Y, Pohl A, Yang D, Kahn M, et al. (January 2011). "A let-7 microRNA-binding site polymorphism in 3'-untranslated region of KRAS gene predicts response in wild-type KRAS patients with metastatic colorectal cancer treated with cetuximab monotherapy". Annals of Oncology. 22 (1): 104–109. doi:10.1093/annonc/mdq315. PMC 8890483. PMID 20603437.
• Zhao Y, Deng C, Wang J, Xiao J, Gatalica Z, Recker RR, Xiao GG (May 2011). "Let-7 family miRNAs regulate estrogen receptor alpha signaling in estrogen receptor positive breast cancer". Breast Cancer Research and Treatment. 127 (1): 69–80. doi:10.1007/s10549-010-0972-2. PMID 20535543. S2CID 29668405.
• Hu G, Zhou R, Liu J, Gong AY, Chen XM (July 2010). "MicroRNA-98 and let-7 regulate expression of suppressor of cytokine signaling 4 in biliary epithelial cells in response to Cryptosporidium parvum infection". The Journal of Infectious Diseases. 202 (1): 125–135. doi:10.1086/653212. PMC 2880649. PMID 20486857.
• Steinemann D, Tauscher M, Praulich I, Niemeyer CM, Flotho C, Schlegelberger B (September 2010). "Mutations in the let-7 binding site - a mechanism of RAS activation in juvenile myelomonocytic leukemia?". Haematologica. 95 (9): 1616. doi:10.3324/haematol.2010.024984. PMC 2930968. PMID 20460640.
• Wong TS, Man OY, Tsang CM, Tsao SW, Tsang RK, Chan JY, et al. (March 2011). "MicroRNA let-7 suppresses nasopharyngeal carcinoma cells proliferation through downregulating c-Myc expression". Journal of Cancer Research and Clinical Oncology. 137 (3): 415–422. doi:10.1007/s00432-010-0898-4. PMC 3036828. PMID 20440510.
• Shimizu S, Takehara T, Hikita H, Kodama T, Miyagi T, Hosui A, et al. (May 2010). "The let-7 family of microRNAs inhibits Bcl-xL expression and potentiates sorafenib-induced apoptosis in human hepatocellular carcinoma". Journal of Hepatology. 52 (5): 698–704. doi:10.1016/j.jhep.2009.12.024. PMID 20347499.
• Jakymiw A, Patel RS, Deming N, Bhattacharyya I, Shah P, Lamont RJ, et al. (June 2010). "Overexpression of dicer as a result of reduced let-7 MicroRNA levels contributes to increased cell proliferation of oral cancer cells". Genes, Chromosomes & Cancer. 49 (6): 549–559. doi:10.1002/gcc.20765. PMC 2859695. PMID 20232482.
• Koh W, Sheng CT, Tan B, Lee QY, Kuznetsov V, Kiang LS, Tanavde V (February 2010). "Analysis of deep sequencing microRNA expression profile from human embryonic stem cells derived mesenchymal stem cells reveals possible role of let-7 microRNA family in downstream targeting of hepatic nuclear factor 4 alpha". BMC Genomics. 11 (Suppl 1): S6. doi:10.1186/1471-2164-11-S1-S6. PMC 2822534. PMID 20158877.
• Balzer E, Heine C, Jiang Q, Lee VM, Moss EG (March 2010). "LIN28 alters cell fate succession and acts independently of the let-7 microRNA during neurogliogenesis in vitro". Development. 137 (6): 891–900. doi:10.1242/dev.042895. PMID 20179095.
• Graziano F, Canestrari E, Loupakis F, Ruzzo A, Galluccio N, Santini D, et al. (October 2010). "Genetic modulation of the Let-7 microRNA binding to KRAS 3'-untranslated region and survival of metastatic colorectal cancer patients treated with salvage cetuximab-irinotecan". The Pharmacogenomics Journal. 10 (5): 458–464. doi:10.1038/tpj.2010.9. PMID 20177422.
• Klemke M, Meyer A, Hashemi Nezhad M, Belge G, Bartnitzke S, Bullerdiek J (January 2010). "Loss of let-7 binding sites resulting from truncations of the 3' untranslated region of HMGA2 mRNA in uterine leiomyomas". Cancer Genetics and Cytogenetics. 196 (2): 119–123. doi:10.1016/j.cancergencyto.2009.09.021. PMID 20082846.
• Oh JS, Kim JJ, Byun JY, Kim IA (January 2010). "Lin28-let7 modulates radiosensitivity of human cancer cells with activation of K-Ras". International Journal of Radiation Oncology, Biology, Physics. 76 (1): 5–8. doi:10.1016/j.ijrobp.2009.08.028. PMID 20005451.
• Mu G, Liu H, Zhou F, Xu X, Jiang H, Wang Y, Qu Y (April 2010). "Correlation of overexpression of HMGA1 and HMGA2 with poor tumor differentiation, invasion, and proliferation associated with let-7 down-regulation in retinoblastomas". Human Pathology. 41 (4): 493–502. doi:10.1016/j.humpath.2009.08.022. PMID 20004941.
• Trang P, Medina PP, Wiggins JF, Ruffino L, Kelnar K, Omotola M, et al. (March 2010). "Regression of murine lung tumors by the let-7 microRNA". Oncogene. 29 (11): 1580–1587. doi:10.1038/onc.2009.445. PMC 2841713. PMID 19966857.
• Ricarte-Filho JC, Fuziwara CS, Yamashita AS, Rezende E, da-Silva MJ, Kimura ET (December 2009). "Effects of let-7 microRNA on Cell Growth and Differentiation of Papillary Thyroid Cancer". Translational Oncology. 2 (4): 236–241. doi:10.1593/tlo.09151. PMC 2781070. PMID 19956384.
• Noh SJ, Miller SH, Lee YT, Goh SH, Marincola FM, Stroncek DF, et al. (November 2009). "Let-7 microRNAs are developmentally regulated in circulating human erythroid cells". Journal of Translational Medicine. 7: 98. doi:10.1186/1479-5876-7-98. PMC 2792219. PMID 19939273.
• Rybak A, Fuchs H, Hadian K, Smirnova L, Wulczyn EA, Michel G, et al. (December 2009). "The let-7 target gene mouse lin-41 is a stem cell specific E3 ubiquitin ligase for the miRNA pathway protein Ago2". Nature Cell Biology. 11 (12): 1411–1420. doi:10.1038/ncb1987. PMID 19898466. S2CID 10902783.
• Iliopoulos D, Hirsch HA, Struhl K (November 2009). "An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation". Cell. 139 (4): 693–706. doi:10.1016/j.cell.2009.10.014. PMC 2783826. PMID 19878981.
• Hammell CM, Karp X, Ambros V (November 2009). "A feedback circuit involving let-7-family miRNAs and DAF-12 integrates environmental signals and developmental timing in Caenorhabditis elegans". Proceedings of the National Academy of Sciences of the United States of America. 106 (44): 18668–18673. Bibcode:2009PNAS..10618668H. doi:10.1073/pnas.0908131106. PMC 2774035. PMID 19828440.
• Boyerinas B, Park SM, Hau A, Murmann AE, Peter ME (March 2010). "The role of let-7 in cell differentiation and cancer". Endocrine-Related Cancer. 17 (1): F19 – F36. doi:10.1677/ERC-09-0184. PMID 19779035.
• Hagan JP, Piskounova E, Gregory RI (October 2009). "Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells". Nature Structural & Molecular Biology. 16 (10): 1021–1025. doi:10.1038/nsmb.1676. PMC 2758923. PMID 19713958.
• Lehrbach NJ, Armisen J, Lightfoot HL, Murfitt KJ, Bugaut A, Balasubramanian S, Miska EA (October 2009). "LIN-28 and the poly(U) polymerase PUP-2 regulate let-7 microRNA processing in Caenorhabditis elegans". Nature Structural & Molecular Biology. 16 (10): 1016–1020. doi:10.1038/nsmb.1675. PMC 2988485. PMID 19713957.
• Li Y, VandenBoom TG, Kong D, Wang Z, Ali S, Philip PA, Sarkar FH (August 2009). "Up-regulation of miR-200 and let-7 by natural agents leads to the reversal of epithelial-to-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells". Cancer Research. 69 (16): 6704–6712. doi:10.1158/0008-5472.CAN-09-1298. PMC 2727571. PMID 19654291.
• Roush SF, Slack FJ (October 2009). "Transcription of the C. elegans let-7 microRNA is temporally regulated by one of its targets, hbl-1". Developmental Biology. 334 (2): 523–534. doi:10.1016/j.ydbio.2009.07.012. PMC 2753757. PMID 19627983.
• Chan SP, Slack FJ (October 2009). "Ribosomal protein RPS-14 modulates let-7 microRNA function in Caenorhabditis elegans". Developmental Biology. 334 (1): 152–160. doi:10.1016/j.ydbio.2009.07.011. PMC 2753218. PMID 19627982.
• Shi G, Perle MA, Mittal K, Chen H, Zou X, Narita M, et al. (September 2009). "Let-7 repression leads to HMGA2 overexpression in uterine leiomyosarcoma". Journal of Cellular and Molecular Medicine. 13 (9B): 3898–3905. doi:10.1111/j.1582-4934.2008.00541.x. PMC 4516537. PMID 19602040.
• Kim HH, Kuwano Y, Srikantan S, Lee EK, Martindale JL, Gorospe M (August 2009). "HuR recruits let-7/RISC to repress c-Myc expression". Genes & Development. 23 (15): 1743–1748. doi:10.1101/gad.1812509. PMC 2720259. PMID 19574298.
• Wang X, Hulshizer RL, Erickson-Johnson MR, Flynn HC, Jenkins RB, Lloyd RV, Oliveira AM (August 2009). "Identification of novel HMGA2 fusion sequences in lipoma: evidence that deletion of let-7 miRNA consensus binding site 1 in the HMGA2 3' UTR is not critical for HMGA2 transcriptional upregulation". Genes, Chromosomes & Cancer. 48 (8): 673–678. doi:10.1002/gcc.20674. PMID 19431195. S2CID 5328884.
• Christensen BC, Moyer BJ, Avissar M, Ouellet LG, Plaza SL, McClean MD, et al. (June 2009). "A let-7 microRNA-binding site polymorphism in the KRAS 3' UTR is associated with reduced survival in oral cancers". Carcinogenesis. 30 (6): 1003–1007. doi:10.1093/carcin/bgp099. PMC 2691138. PMID 19380522.
• Slack F (June 2009). "let-7 microRNA reduces tumor growth". Cell Cycle. 8 (12): 1823. doi:10.4161/cc.8.12.8639. PMID 19377282.
• Sun T, Fu M, Bookout AL, Kliewer SA, Mangelsdorf DJ (June 2009). "MicroRNA let-7 regulates 3T3-L1 adipogenesis". Molecular Endocrinology. 23 (6): 925–931. doi:10.1210/me.2008-0298. PMC 2691679. PMID 19324969.
• Torrisani J, Bournet B, du Rieu MC, Bouisson M, Souque A, Escourrou J, et al. (August 2009). "let-7 MicroRNA transfer in pancreatic cancer-derived cells inhibits in vitro cell proliferation but fails to alter tumor progression". Human Gene Therapy. 20 (8): 831–844. doi:10.1089/hum.2008.134. PMID 19323605.
• Peter ME (March 2009). "Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression". Cell Cycle. 8 (6): 843–852. doi:10.4161/cc.8.6.7907. PMC 2688687. PMID 19221491.
• Chang TC, Zeitels LR, Hwang HW, Chivukula RR, Wentzel EA, Dews M, et al. (March 2009). "Lin-28B transactivation is necessary for Myc-mediated let-7 repression and proliferation". Proceedings of the National Academy of Sciences of the United States of America. 106 (9): 3384–3389. Bibcode:2009PNAS..106.3384C. doi:10.1073/pnas.0808300106. PMC 2651245. PMID 19211792.
• Rahman MM, Qian ZR, Wang EL, Sultana R, Kudo E, Nakasono M, et al. (February 2009). "Frequent overexpression of HMGA1 and 2 in gastroenteropancreatic neuroendocrine tumours and its relationship to let-7 downregulation". British Journal of Cancer. 100 (3): 501–510. doi:10.1038/sj.bjc.6604883. PMC 2658538. PMID 19156147.
• Dangi-Garimella S, Yun J, Eves EM, Newman M, Erkeland SJ, Hammond SM, et al. (February 2009). "Raf kinase inhibitory protein suppresses a metastasis signalling cascade involving LIN28 and let-7". The EMBO Journal. 28 (4): 347–358. doi:10.1038/emboj.2008.294. PMC 2646152. PMID 19153603.
• Qian ZR, Asa SL, Siomi H, Siomi MC, Yoshimoto K, Yamada S, et al. (March 2009). "Overexpression of HMGA2 relates to reduction of the let-7 and its relationship to clinicopathological features in pituitary adenomas". Modern Pathology. 22 (3): 431–441. doi:10.1038/modpathol.2008.202. PMID 19136928.
• Legesse-Miller A, Elemento O, Pfau SJ, Forman JJ, Tavazoie S, Coller HA (March 2009). "let-7 Overexpression leads to an increased fraction of cells in G2/M, direct down-regulation of Cdc34, and stabilization of Wee1 kinase in primary fibroblasts". The Journal of Biological Chemistry. 284 (11): 6605–6609. doi:10.1074/jbc.C900002200. PMC 2652271. PMID 19126550.
• Maller Schulman BR, Liang X, Stahlhut C, DelConte C, Stefani G, Slack FJ (December 2008). "The let-7 microRNA target gene, Mlin41/Trim71 is required for mouse embryonic survival and neural tube closure". Cell Cycle. 7 (24): 3935–3942. doi:10.4161/cc.7.24.7397. PMC 2895810. PMID 19098426.
• Heo I, Joo C, Cho J, Ha M, Han J, Kim VN (October 2008). "Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA". Molecular Cell. 32 (2): 276–284. doi:10.1016/j.molcel.2008.09.014. PMID 18951094.
• Chin LJ, Ratner E, Leng S, Zhai R, Nallur S, Babar I, et al. (October 2008). "A SNP in a let-7 microRNA complementary site in the KRAS 3' untranslated region increases non-small cell lung cancer risk". Cancer Research. 68 (20): 8535–8540. doi:10.1158/0008-5472.CAN-08-2129. PMC 2672193. PMID 18922928.
• Andachi Y (November 2008). "A novel biochemical method to identify target genes of individual microRNAs: identification of a new Caenorhabditis elegans let-7 target". RNA. 14 (11): 2440–2451. doi:10.1261/rna.1139508. PMC 2578851. PMID 18824511.
• Ding XC, Slack FJ, Grosshans H (October 2008). "The let-7 microRNA interfaces extensively with the translation machinery to regulate cell differentiation". Cell Cycle. 7 (19): 3083–3090. doi:10.4161/cc.7.19.6778. PMC 2887667. PMID 18818519.
• Forman JJ, Legesse-Miller A, Coller HA (September 2008). "A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence". Proceedings of the National Academy of Sciences of the United States of America. 105 (39): 14879–14884. Bibcode:2008PNAS..10514879F. doi:10.1073/pnas.0803230105. PMC 2567461. PMID 18812516.
• Roush S, Slack FJ (October 2008). "The let-7 family of microRNAs". Trends in Cell Biology. 18 (10): 505–516. doi:10.1016/j.tcb.2008.07.007. PMID 18774294.
• Tennessen JM, Thummel CS (August 2008). "Developmental timing: let-7 function conserved through evolution". Current Biology. 18 (16): R707 – R708. Bibcode:2008CBio...18.R707T. doi:10.1016/j.cub.2008.07.013. PMC 2583239. PMID 18727906.
• Chan SP, Ramaswamy G, Choi EY, Slack FJ (October 2008). "Identification of specific let-7 microRNA binding complexes in Caenorhabditis elegans". RNA. 14 (10): 2104–2114. doi:10.1261/rna.551208. PMC 2553747. PMID 18719242.
• Tokumaru S, Suzuki M, Yamada H, Nagino M, Takahashi T (November 2008). "let-7 regulates Dicer expression and constitutes a negative feedback loop". Carcinogenesis. 29 (11): 2073–2077. doi:10.1093/carcin/bgn187. PMID 18700235.
• Büssing I, Slack FJ, Grosshans H (September 2008). "let-7 microRNAs in development, stem cells and cancer". Trends in Molecular Medicine. 14 (9): 400–409. doi:10.1016/j.molmed.2008.07.001. PMID 18674967.
• Jérôme T, Laurie P, Louis B, Pierre C (June 2007). "Enjoy the Silence: The Story of let-7 MicroRNA and Cancer". Current Genomics. 8 (4): 229–233. doi:10.2174/138920207781386933. PMC 2430685. PMID 18645597.
• Reid JG, Nagaraja AK, Lynn FC, Drabek RB, Muzny DM, Shaw CA, et al. (October 2008). "Mouse let-7 miRNA populations exhibit RNA editing that is constrained in the 5'-seed/ cleavage/anchor regions and stabilize predicted mmu-let-7a:mRNA duplexes". Genome Research. 18 (10): 1571–1581. doi:10.1101/gr.078246.108. PMC 2556275. PMID 18614752.
• Rybak A, Fuchs H, Smirnova L, Brandt C, Pohl EE, Nitsch R, Wulczyn FG (August 2008). "A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment". Nature Cell Biology. 10 (8): 987–993. doi:10.1038/ncb1759. PMID 18604195. S2CID 12188484.
• Edge RE, Falls TJ, Brown CW, Lichty BD, Atkins H, Bell JC (August 2008). "A let-7 MicroRNA-sensitive vesicular stomatitis virus demonstrates tumor-specific replication". Molecular Therapy. 16 (8): 1437–1443. doi:10.1038/mt.2008.130. hdl:10393/12831. PMID 18560417.
• Sokol NS, Xu P, Jan YN, Ambros V (June 2008). "Drosophila let-7 microRNA is required for remodeling of the neuromusculature during metamorphosis". Genes & Development. 22 (12): 1591–1596. doi:10.1101/gad.1671708. PMC 2428057. PMID 18559475.
• Motoyama K, Inoue H, Nakamura Y, Uetake H, Sugihara K, Mori M (April 2008). "Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family". Clinical Cancer Research. 14 (8): 2334–2340. doi:10.1158/1078-0432.CCR-07-4667. PMID 18413822.
• Boyerinas B, Park SM, Shomron N, Hedegaard MM, Vinther J, Andersen JS, et al. (April 2008). "Identification of let-7-regulated oncofetal genes". Cancer Research. 68 (8): 2587–2591. doi:10.1158/0008-5472.CAN-08-0264. PMID 18413726.
• Peng Y, Laser J, Shi G, Mittal K, Melamed J, Lee P, Wei JJ (April 2008). "Antiproliferative effects by Let-7 repression of high-mobility group A2 in uterine leiomyoma". Molecular Cancer Research. 6 (4): 663–673. doi:10.1158/1541-7786.MCR-07-0370. PMID 18403645.
• Garfield D (May 2008). "let-7 microRNA expression and the distinction between nonmucinous and mucinous bronchioloalveolar carcinomas". Lung Cancer. 60 (2): 307. doi:10.1016/j.lungcan.2008.02.010. PMID 18395292.
• Dröge P, Davey CA (January 2008). "Do cells let-7 determine stemness?". Cell Stem Cell. 2 (1): 8–9. doi:10.1016/j.stem.2007.12.003. PMID 18371414.
• Solomon A, Mian Y, Ortega-Cava C, Liu VW, Gurumurthy CB, Naramura M, et al. (April 2008). "Upregulation of the let-7 microRNA with precocious development in lin-12/Notch hypermorphic Caenorhabditis elegans mutants". Developmental Biology. 316 (2): 191–199. doi:10.1016/j.ydbio.2007.12.046. PMC 2390880. PMID 18334253.
• Kumar MS, Erkeland SJ, Pester RE, Chen CY, Ebert MS, Sharp PA, Jacks T (March 2008). "Suppression of non-small cell lung tumor development by the let-7 microRNA family". Proceedings of the National Academy of Sciences of the United States of America. 105 (10): 3903–3908. Bibcode:2008PNAS..105.3903K. doi:10.1073/pnas.0712321105. PMC 2268826. PMID 18308936.
• Cevec M, Thibaudeau C, Plavec J (April 2008). "Solution structure of a let-7 miRNA:lin-41 mRNA complex from C. elegans". Nucleic Acids Research. 36 (7): 2330–2337. doi:10.1093/nar/gkn088. PMC 2367737. PMID 18296482.
• Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, et al. (December 2007). "let-7 regulates self renewal and tumorigenicity of breast cancer cells". Cell. 131 (6): 1109–1123. doi:10.1016/j.cell.2007.10.054. PMID 18083101.
• O'Farrell F, Esfahani SS, Engström Y, Kylsten P (January 2008). "Regulation of the Drosophila lin-41 homologue dappled by let-7 reveals conservation of a regulatory mechanism within the LIN-41 subclade". Developmental Dynamics. 237 (1): 196–208. doi:10.1002/dvdy.21396. PMID 18069688.
• Park SM, Shell S, Radjabi AR, Schickel R, Feig C, Boyerinas B, et al. (November 2007). "Let-7 prevents early cancer progression by suppressing expression of the embryonic gene HMGA2". Cell Cycle. 6 (21): 2585–2590. doi:10.4161/cc.6.21.4845. PMID 17957144.
• Lin YC, Hsieh LC, Kuo MW, Yu J, Kuo HH, Lo WL, et al. (November 2007). "Human TRIM71 and its nematode homologue are targets of let-7 microRNA and its zebrafish orthologue is essential for development". Molecular Biology and Evolution. 24 (11): 2525–2534. doi:10.1093/molbev/msm195. PMID 17890240.
• Tsonis PA, Call MK, Grogg MW, Sartor MA, Taylor RR, Forge A, et al. (November 2007). "MicroRNAs and regeneration: Let-7 members as potential regulators of dedifferentiation in lens and inner ear hair cell regeneration of the adult newt". Biochemical and Biophysical Research Communications. 362 (4): 940–945. doi:10.1016/j.bbrc.2007.08.077. PMC 2683343. PMID 17765873.
• Inamura K, Togashi Y, Nomura K, Ninomiya H, Hiramatsu M, Satoh Y, et al. (December 2007). "let-7 microRNA expression is reduced in bronchioloalveolar carcinoma, a non-invasive carcinoma, and is not correlated with prognosis". Lung Cancer. 58 (3): 392–396. doi:10.1016/j.lungcan.2007.07.013. PMID 17728006.
• Salzman DW, Shubert-Coleman J, Furneaux H (November 2007). "P68 RNA helicase unwinds the human let-7 microRNA precursor duplex and is required for let-7-directed silencing of gene expression". The Journal of Biological Chemistry. 282 (45): 32773–32779. doi:10.1074/jbc.M705054200. PMID 17724023.
• Wakiyama M, Takimoto K, Ohara O, Yokoyama S (August 2007). "Let-7 microRNA-mediated mRNA deadenylation and translational repression in a mammalian cell-free system". Genes & Development. 21 (15): 1857–1862. doi:10.1101/gad.1566707. PMC 1935024. PMID 17671087.
• Liu S, Xia Q, Zhao P, Cheng T, Hong K, Xiang Z (July 2007). "Characterization and expression patterns of let-7 microRNA in the silkworm (Bombyx mori)". BMC Developmental Biology. 7: 88. doi:10.1186/1471-213X-7-88. PMC 1976426. PMID 17651473.
• Lee YS, Dutta A (May 2007). "The tumor suppressor microRNA let-7 represses the HMGA2 oncogene". Genes & Development. 21 (9): 1025–1030. doi:10.1101/gad.1540407. PMC 1855228. PMID 17437991.
• Nolde MJ, Saka N, Reinert KL, Slack FJ (May 2007). "The Caenorhabditis elegans pumilio homolog, puf-9, is required for the 3'UTR-mediated repression of the let-7 microRNA target gene, hbl-1". Developmental Biology. 305 (2): 551–563. doi:10.1016/j.ydbio.2007.02.040. PMC 2096746. PMID 17412319.
• Hayes GD, Ruvkun G (2006). "Misexpression of the Caenorhabditis elegans miRNA let-7 is sufficient to drive developmental programs". Cold Spring Harbor Symposia on Quantitative Biology. 71: 21–27. doi:10.1101/sqb.2006.71.018. PMID 17381276.
• Hayes GD, Frand AR, Ruvkun G (December 2006). "The mir-84 and let-7 paralogous microRNA genes of Caenorhabditis elegans direct the cessation of molting via the conserved nuclear hormone receptors NHR-23 and NHR-25". Development. 133 (23): 4631–4641. doi:10.1242/dev.02655. PMID 17065234.
• Akao Y, Nakagawa Y, Naoe T (May 2006). "let-7 microRNA functions as a potential growth suppressor in human colon cancer cells". Biological & Pharmaceutical Bulletin. 29 (5): 903–906. doi:10.1248/bpb.29.903. PMID 16651716.
• Schulman BR, Esquela-Kerscher A, Slack FJ (December 2005). "Reciprocal expression of lin-41 and the microRNAs let-7 and mir-125 during mouse embryogenesis". Developmental Dynamics. 234 (4): 1046–1054. doi:10.1002/dvdy.20599. PMC 2596717. PMID 16247770.
• Esquela-Kerscher A, Johnson SM, Bai L, Saito K, Partridge J, Reinert KL, Slack FJ (December 2005). "Post-embryonic expression of C. elegans microRNAs belonging to the lin-4 and let-7 families in the hypodermis and the reproductive system". Developmental Dynamics. 234 (4): 868–877. doi:10.1002/dvdy.20572. PMC 2572564. PMID 16217741.
• Li M, Jones-Rhoades MW, Lau NC, Bartel DP, Rougvie AE (September 2005). "Regulatory mutations of mir-48, a C. elegans let-7 family MicroRNA, cause developmental timing defects". Developmental Cell. 9 (3): 415–422. doi:10.1016/j.devcel.2005.08.002. PMID 16139229.
• Abbott AL, Alvarez-Saavedra E, Miska EA, Lau NC, Bartel DP, Horvitz HR, Ambros V (September 2005). "The let-7 MicroRNA family members mir-48, mir-84, and mir-241 function together to regulate developmental timing in Caenorhabditis elegans". Developmental Cell. 9 (3): 403–414. doi:10.1016/j.devcel.2005.07.009. PMC 3969732. PMID 16139228.
• Bagga S, Bracht J, Hunter S, Massirer K, Holtz J, Eachus R, Pasquinelli AE (August 2005). "Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation". Cell. 122 (4): 553–563. doi:10.1016/j.cell.2005.07.031. PMID 16122423.
• Pillai RS, Bhattacharyya SN, Artus CG, Zoller T, Cougot N, Basyuk E, et al. (September 2005). "Inhibition of translational initiation by Let-7 MicroRNA in human cells". Science. 309 (5740): 1573–1576. Bibcode:2005Sci...309.1573P. doi:10.1126/science.1115079. PMID 16081698. S2CID 42472697.
• Grosshans H, Johnson T, Reinert KL, Gerstein M, Slack FJ (March 2005). "The temporal patterning microRNA let-7 regulates several transcription factors at the larval to adult transition in C. elegans". Developmental Cell. 8 (3): 321–330. doi:10.1016/j.devcel.2004.12.019. PMID 15737928.
• Kloosterman WP, Wienholds E, Ketting RF, Plasterk RH (2004). "Substrate requirements for let-7 function in the developing zebrafish embryo". Nucleic Acids Research. 32 (21): 6284–6291. doi:10.1093/nar/gkh968. PMC 535676. PMID 15585662.
• Bracht J, Hunter S, Eachus R, Weeks P, Pasquinelli AE (October 2004). "Trans-splicing and polyadenylation of let-7 microRNA primary transcripts". RNA. 10 (10): 1586–1594. doi:10.1261/rna.7122604. PMC 1370645. PMID 15337850.
• Vella MC, Choi EY, Lin SY, Reinert K, Slack FJ (January 2004). "The C. elegans microRNA let-7 binds to imperfect let-7 complementary sites from the lin-41 3'UTR". Genes & Development. 18 (2): 132–137. doi:10.1101/gad.1165404. PMC 324419. PMID 14729570.
• Basyuk E, Suavet F, Doglio A, Bordonné R, Bertrand E (November 2003). "Human let-7 stem-loop precursors harbor features of RNase III cleavage products". Nucleic Acids Research. 31 (22): 6593–6597. doi:10.1093/nar/gkg855. PMC 275551. PMID 14602919.
• Johnson SM, Lin SY, Slack FJ (July 2003). "The time of appearance of the C. elegans let-7 microRNA is transcriptionally controlled utilizing a temporal regulatory element in its promoter". Developmental Biology. 259 (2): 364–379. doi:10.1016/S0012-1606(03)00202-1. PMID 12871707.
• Pasquinelli AE, McCoy A, Jiménez E, Saló E, Ruvkun G, Martindale MQ, Baguñà J (2003). "Expression of the 22 nucleotide let-7 heterochronic RNA throughout the Metazoa: a role in life history evolution?". Evolution & Development. 5 (4): 372–378. doi:10.1046/j.1525-142X.2003.03044.x. PMID 12823453. S2CID 32723915.
• Sempere LF, Dubrovsky EB, Dubrovskaya VA, Berger EM, Ambros V (April 2002). "The expression of the let-7 small regulatory RNA is controlled by ecdysone during metamorphosis in Drosophila melanogaster". Developmental Biology. 244 (1): 170–179. doi:10.1006/dbio.2002.0594. PMID 11900466.
• Hutvágner G, McLachlan J, Pasquinelli AE, Bálint E, Tuschl T, Zamore PD (August 2001). "A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA". Science. 293 (5531): 834–838. doi:10.1126/science.1062961. PMID 11452083. S2CID 6177608.
• Slack FJ, Basson M, Liu Z, Ambros V, Horvitz HR, Ruvkun G (April 2000). "The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor". Molecular Cell. 5 (4): 659–669. doi:10.1016/S1097-2765(00)80245-2. PMID 10882102.
• Lin S, Li H, Mu H, Luo W, Li Y, Jia X, et al. (July 2012). "Let-7b regulates the expression of the growth hormone receptor gene in deletion-type dwarf chickens". BMC Genomics. 13: 306. doi:10.1186/1471-2164-13-306. PMC 3428657. PMID 22781587.
• Shen Y, Wollam J, Magner D, Karalay O, Antebi A (December 2012). "A steroid receptor-microRNA switch regulates life span in response to signals from the gonad". Science. 338 (6113): 1472–1476. Bibcode:2012Sci...338.1472S. doi:10.1126/science.1228967. PMC 3909774. PMID 23239738.

External links

• Page for let-7 microRNA precursor at Rfam
• miRBase family entry for let-7