Junk DNA and the Long Non-coding RNA Twist in Cancer Genetics

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2015 Jan 27

PMID 25619839

Citations 186

Authors

H Ling

K Vincent

M Pichler

R Fodde

I Berindan-Neagoe

F J Slack

G A Calin

Affiliations

Soon will be listed here.

Abstract

The central dogma of molecular biology states that the flow of genetic information moves from DNA to RNA to protein. However, in the last decade this dogma has been challenged by new findings on non-coding RNAs (ncRNAs) such as microRNAs (miRNAs). More recently, long non-coding RNAs (lncRNAs) have attracted much attention due to their large number and biological significance. Many lncRNAs have been identified as mapping to regulatory elements including gene promoters and enhancers, ultraconserved regions and intergenic regions of protein-coding genes. Yet, the biological function and molecular mechanisms of lncRNA in human diseases in general and cancer in particular remain largely unknown. Data from the literature suggest that lncRNA, often via interaction with proteins, functions in specific genomic loci or use their own transcription loci for regulatory activity. In this review, we summarize recent findings supporting the importance of DNA loci in lncRNA function and the underlying molecular mechanisms via cis or trans regulation, and discuss their implications in cancer. In addition, we use the 8q24 genomic locus, a region containing interactive SNPs, DNA regulatory elements and lncRNAs, as an example to illustrate how single-nucleotide polymorphism (SNP) located within lncRNAs may be functionally associated with the individual's susceptibility to cancer.

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References

Ulitsky I, Bartel D . lincRNAs: genomics, evolution, and mechanisms. Cell. 2013; 154(1):26-46. PMC: 3924787. DOI: 10.1016/j.cell.2013.06.020. View

Lee J, Bartolomei M . X-inactivation, imprinting, and long noncoding RNAs in health and disease. Cell. 2013; 152(6):1308-23. DOI: 10.1016/j.cell.2013.02.016. View

Beltran M, Puig I, Pena C, Garcia J, Alvarez A, Pena R . A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition. Genes Dev. 2008; 22(6):756-69. PMC: 2275429. DOI: 10.1101/gad.455708. View

Srikantan V, Zou Z, Petrovics G, Xu L, Augustus M, Davis L . PCGEM1, a prostate-specific gene, is overexpressed in prostate cancer. Proc Natl Acad Sci U S A. 2000; 97(22):12216-21. PMC: 17321. DOI: 10.1073/pnas.97.22.12216. View

Bertucci F, Lagarde A, Ferrari A, Finetti P, Charafe-Jauffret E, Van Laere S . 8q24 Cancer risk allele associated with major metastatic risk in inflammatory breast cancer. PLoS One. 2012; 7(5):e37943. PMC: 3362533. DOI: 10.1371/journal.pone.0037943. View

Sanford J, Wang X, Mort M, VanDuyn N, Cooper D, Mooney S . Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts. Genome Res. 2009; 19(3):381-94. PMC: 2661799. DOI: 10.1101/gr.082503.108. View

Liu Y, Pan S, Liu L, Zhai X, Liu J, Wen J . A genetic variant in long non-coding RNA HULC contributes to risk of HBV-related hepatocellular carcinoma in a Chinese population. PLoS One. 2012; 7(4):e35145. PMC: 3320879. DOI: 10.1371/journal.pone.0035145. View

Du Z, Fei T, Verhaak R, Su Z, Zhang Y, Brown M . Integrative genomic analyses reveal clinically relevant long noncoding RNAs in human cancer. Nat Struct Mol Biol. 2013; 20(7):908-13. PMC: 3702647. DOI: 10.1038/nsmb.2591. View

Hnisz D, Abraham B, Lee T, Lau A, Saint-Andre V, Sigova A . Super-enhancers in the control of cell identity and disease. Cell. 2013; 155(4):934-47. PMC: 3841062. DOI: 10.1016/j.cell.2013.09.053. View

10.

Bertani S, Sauer S, Bolotin E, Sauer F . The noncoding RNA Mistral activates Hoxa6 and Hoxa7 expression and stem cell differentiation by recruiting MLL1 to chromatin. Mol Cell. 2011; 43(6):1040-6. PMC: 3176448. DOI: 10.1016/j.molcel.2011.08.019. View

11.

Tuupanen S, Turunen M, Lehtonen R, Hallikas O, Vanharanta S, Kivioja T . The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling. Nat Genet. 2009; 41(8):885-90. DOI: 10.1038/ng.406. View

12.

Hindorff L, Sethupathy P, Junkins H, Ramos E, Mehta J, Collins F . Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci U S A. 2009; 106(23):9362-7. PMC: 2687147. DOI: 10.1073/pnas.0903103106. View

13.

Prensner J, Iyer M, Balbin O, Dhanasekaran S, Cao Q, Brenner J . Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression. Nat Biotechnol. 2011; 29(8):742-9. PMC: 3152676. DOI: 10.1038/nbt.1914. View

14.

Chen D, Zhang Z, Mao C, Zhou Y, Yu L, Yin Y . ANRIL inhibits p15(INK4b) through the TGFβ1 signaling pathway in human esophageal squamous cell carcinoma. Cell Immunol. 2014; 289(1-2):91-6. DOI: 10.1016/j.cellimm.2014.03.015. View

15.

Batista P, Chang H . Long noncoding RNAs: cellular address codes in development and disease. Cell. 2013; 152(6):1298-307. PMC: 3651923. DOI: 10.1016/j.cell.2013.02.012. View

16.

Yakovchuk P, Goodrich J, Kugel J . B2 RNA and Alu RNA repress transcription by disrupting contacts between RNA polymerase II and promoter DNA within assembled complexes. Proc Natl Acad Sci U S A. 2009; 106(14):5569-74. PMC: 2667051. DOI: 10.1073/pnas.0810738106. View

17.

Wang K, Chang H . Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011; 43(6):904-14. PMC: 3199020. DOI: 10.1016/j.molcel.2011.08.018. View

18.

Ogawa Y, Sun B, Lee J . Intersection of the RNA interference and X-inactivation pathways. Science. 2008; 320(5881):1336-41. PMC: 2584363. DOI: 10.1126/science.1157676. View

19.

Wang K, Yang Y, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y . A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature. 2011; 472(7341):120-4. PMC: 3670758. DOI: 10.1038/nature09819. View

20.

Martin L, Meier M, Lyons S, Sit R, Marzluff W, Quake S . Systematic reconstruction of RNA functional motifs with high-throughput microfluidics. Nat Methods. 2012; 9(12):1192-4. PMC: 3863600. DOI: 10.1038/nmeth.2225. View