A Network-biology Perspective of MicroRNA Function and Dysfunction in Cancer

Overview

Journal Nat Rev Genet

Specialty Genetics

Date 2016 Nov 8

PMID 27795564

Citations 362

Authors

Cameron P Bracken

Hamish S Scott

Gregory J Goodall

Affiliations

Soon will be listed here.

Abstract

MicroRNAs (miRNAs) participate in most aspects of cellular differentiation and homeostasis, and consequently have roles in many pathologies, including cancer. These small non-coding RNAs exert their effects in the context of complex regulatory networks, often made all the more extensive by the inclusion of transcription factors as their direct targets. In recent years, the increased availability of gene expression data and the development of methodologies that profile miRNA targets en masse have fuelled our understanding of miRNA functions, and of the sources and consequences of miRNA dysregulation. Advances in experimental and computational approaches are revealing not just cancer pathways controlled by single miRNAs but also intermeshed regulatory networks controlled by multiple miRNAs, which often engage in reciprocal feedback interactions with the targets that they regulate.

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References

Shirdel E, Xie W, Mak T, Jurisica I . NAViGaTing the micronome--using multiple microRNA prediction databases to identify signalling pathway-associated microRNAs. PLoS One. 2011; 6(2):e17429. PMC: 3045450. DOI: 10.1371/journal.pone.0017429. View

Wang X, Ren H, Zhao T, Ma W, Dong J, Zhang S . Single nucleotide polymorphism in the microRNA-199a binding site of HIF1A gene is associated with pancreatic ductal adenocarcinoma risk and worse clinical outcomes. Oncotarget. 2016; 7(12):13717-29. PMC: 4924673. DOI: 10.18632/oncotarget.7263. View

Korpal M, Ell B, Buffa F, Ibrahim T, Blanco M, Celia-Terrassa T . Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nat Med. 2011; 17(9):1101-8. PMC: 3169707. DOI: 10.1038/nm.2401. View

Shan S, Fang L, Shatseva T, Rutnam Z, Yang X, Du W . Mature miR-17-5p and passenger miR-17-3p induce hepatocellular carcinoma by targeting PTEN, GalNT7 and vimentin in different signal pathways. J Cell Sci. 2013; 126(Pt 6):1517-30. DOI: 10.1242/jcs.122895. View

Helwak A, Kudla G, Dudnakova T, Tollervey D . Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding. Cell. 2013; 153(3):654-65. PMC: 3650559. DOI: 10.1016/j.cell.2013.03.043. View

Gerstein M, Kundaje A, Hariharan M, Landt S, Yan K, Cheng C . Architecture of the human regulatory network derived from ENCODE data. Nature. 2012; 489(7414):91-100. PMC: 4154057. DOI: 10.1038/nature11245. View

Saunders M, Liang H, Li W . Human polymorphism at microRNAs and microRNA target sites. Proc Natl Acad Sci U S A. 2007; 104(9):3300-5. PMC: 1805605. DOI: 10.1073/pnas.0611347104. View

Hsu C, Juan H, Huang H . Characterization of microRNA-regulated protein-protein interaction network. Proteomics. 2008; 8(10):1975-9. DOI: 10.1002/pmic.200701004. View

Grun D, Wang Y, Langenberger D, Gunsalus K, Rajewsky N . microRNA target predictions across seven Drosophila species and comparison to mammalian targets. PLoS Comput Biol. 2005; 1(1):e13. PMC: 1183519. DOI: 10.1371/journal.pcbi.0010013. View

10.

Plass C, Pfister S, Lindroth A, Bogatyrova O, Claus R, Lichter P . Mutations in regulators of the epigenome and their connections to global chromatin patterns in cancer. Nat Rev Genet. 2013; 14(11):765-80. DOI: 10.1038/nrg3554. View

11.

Ma Y, Zhang P, Wang F, Zhang H, Yang Y, Shi C . Elevated oncofoetal miR-17-5p expression regulates colorectal cancer progression by repressing its target gene P130. Nat Commun. 2012; 3:1291. DOI: 10.1038/ncomms2276. View

12.

Yang J, Li J, Shao P, Zhou H, Chen Y, Qu L . starBase: a database for exploring microRNA-mRNA interaction maps from Argonaute CLIP-Seq and Degradome-Seq data. Nucleic Acids Res. 2010; 39(Database issue):D202-9. PMC: 3013664. DOI: 10.1093/nar/gkq1056. View

13.

Krishnan K, Steptoe A, Martin H, Wani S, Nones K, Waddell N . MicroRNA-182-5p targets a network of genes involved in DNA repair. RNA. 2012; 19(2):230-42. PMC: 3543090. DOI: 10.1261/rna.034926.112. View

14.

Sandberg R, Neilson J, Sarma A, Sharp P, Burge C . Proliferating cells express mRNAs with shortened 3' untranslated regions and fewer microRNA target sites. Science. 2008; 320(5883):1643-7. PMC: 2587246. DOI: 10.1126/science.1155390. View

15.

Guo H, Ingolia N, Weissman J, Bartel D . Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010; 466(7308):835-40. PMC: 2990499. DOI: 10.1038/nature09267. View

16.

Steinfeld I, Navon R, Ach R, Yakhini Z . miRNA target enrichment analysis reveals directly active miRNAs in health and disease. Nucleic Acids Res. 2012; 41(3):e45. PMC: 3561970. DOI: 10.1093/nar/gks1142. View

17.

Wang X . Composition of seed sequence is a major determinant of microRNA targeting patterns. Bioinformatics. 2014; 30(10):1377-83. PMC: 4016705. DOI: 10.1093/bioinformatics/btu045. View

18.

Mori M, Triboulet R, Mohseni M, Schlegelmilch K, Shrestha K, Camargo F . Hippo signaling regulates microprocessor and links cell-density-dependent miRNA biogenesis to cancer. Cell. 2014; 156(5):893-906. PMC: 3982296. DOI: 10.1016/j.cell.2013.12.043. View

19.

Wang Y, Xu Z, Jiang J, Xu C, Kang J, Xiao L . Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal. Dev Cell. 2013; 25(1):69-80. DOI: 10.1016/j.devcel.2013.03.002. View

20.

Kanehisa M, Goto S . KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 1999; 28(1):27-30. PMC: 102409. DOI: 10.1093/nar/28.1.27. View