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Post-transcriptional regulation of long noncoding RNAs in cancer

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  • Published:
Tumor Biology

Abstract

It is a great surprise that the genomes of mammals and other eukaryotes harbor many thousands of long noncoding RNAs (lncRNAs). Although these long noncoding transcripts were once considered to be simply transcriptional noise or cloning artifacts, multiple studies have suggested that lncRNAs are emerging as new players in diverse human diseases, especially in cancer, and that the molecular mechanisms of lncRNAs need to be elucidated. More recently, evidence has begun to accumulate describing the complex post-transcriptional regulation in which lncRNAs are involved. It was reported that lncRNAs can be implicated in degradation, translation, pre-messenger RNA (mRNA) splicing, and protein activities and even as microRNAs (miRNAs) sponges in both a sequence-dependent and sequence-independent manner. In this review, we present an updated vision of lncRNAs and summarize the mechanism of post-transcriptional regulation by lncRNAs, providing new insight into the functional cellular roles that they may play in human diseases, with a particular focus on cancers.

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Abbreviations

lncRNAs:

Long noncoding RNAs

miRNA:

MicroRNA

ceRNA:

Competitive endogenous RNA

siRNAs:

Small interfering RNAs

piRNAs:

Piwi-associated RNAs

Xist:

X inactive specific transcript

HOTAIR:

Hox transcript antisense intergenic RNA

MREs:

MicroRNA response elements

HULC:

Highly upregulated in liver cancer

HCC:

Hepatocellular carcinoma

PTCSC3:

Papillary thyroid carcinoma susceptibility candidate 3

PTC:

Papillary thyroid carcinoma

snRNPs:

Small nuclear ribonucleoproteins

hnRNPs:

Heterogeneous nuclear ribonucleoproteins

MALAT1:

Metastasis-associated lung adenocarcinoma transcript 1

NAT:

Natural antisense transcript

UTR:

Untranslated region

EMT:

Epithelial–mesenchymal transition

CHO:

Chinese hamster ovary

Cdk6:

Cyclin-dependent kinase 6

SMD:

Staufen 1-mediated mRNA decay

1/2-sbsRNAs:

Half-STAU1-binding site RNAs

TINCR:

Terminal differentiation-induced ncRNA

RPA:

RNase protection assay

Uchl1:

Ubiquitin carboxyterminal hydrolase L1

treRNA:

Translational regulatory lncRNA

RNP:

Ribonucleoprotein

lncRNA-LET:

LncRNA Low Expression in Tumor

H19:

H19, imprinted maternally expressed transcript

PTENP1:

Phosphatase and tensin homolog pseudogene 1

References

  1. Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, et al. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res. 2012;22(9):1775–89. doi:10.1101/gr.132159.111.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409(6822):860–921. doi:10.1038/35057062.

    CAS  PubMed  Google Scholar 

  3. Stein LD. Human genome: end of the beginning. Nature. 2004;431(7011):915–6. doi:10.1038/431915a.

    CAS  PubMed  Google Scholar 

  4. Costa FF. Non-coding RNAs: meet thy masters. BioEssays : News Rev Mol Cell Dev Biol. 2010;32(7):599–608. doi:10.1002/bies.200900112.

    CAS  Google Scholar 

  5. Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, et al. Landscape of transcription in human cells. Nature. 2012;489(7414):101–8. doi:10.1038/nature11233.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Gibb EA, Brown CJ, Lam WL. The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 2011;10:38. doi:10.1186/1476-4598-10-38.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10(3):155–9. doi:10.1038/nrg2521.

    CAS  PubMed  Google Scholar 

  8. Carthew RW, Sontheimer EJ. Origins and mechanisms of miRNAs and siRNAs. Cell. 2009;136(4):642–55. doi:10.1016/j.cell.2009.01.035.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Mo YY. MicroRNA regulatory networks and human disease. Cell Mol Life Sci : CMLS. 2012;69(21):3529–31. doi:10.1007/s00018-012-1123-1.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011;43(6):904–14. doi:10.1016/j.molcel.2011.08.018.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Wilusz JE, Sunwoo H, Spector DL. Long noncoding RNAs: functional surprises from the RNA world. Genes Dev. 2009;23(13):1494–504. doi:10.1101/gad.1800909.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Brannan CI, Dees EC, Ingram RS, Tilghman SM. The product of the H19 gene may function as an RNA. Mol Cell Biol. 1990;10(1):28–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Brockdorff N, Ashworth A, Kay GF, McCabe VM, Norris DP, Cooper PJ, et al. The product of the mouse Xist gene is a 15 kb inactive X-specific transcript containing no conserved ORF and located in the nucleus. Cell. 1992;71(3):515–26.

    CAS  PubMed  Google Scholar 

  14. Ulitsky I, Shkumatava A, Jan CH, Sive H, Bartel DP. Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution. Cell. 2011;147(7):1537–50. doi:10.1016/j.cell.2011.11.055.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Kornienko AE, Guenzl PM, Barlow DP, Pauler FM. Gene regulation by the act of long non-coding RNA transcription. BMC Biol. 2013;11:59. doi:10.1186/1741-7007-11-59.

    PubMed  PubMed Central  Google Scholar 

  16. Tuck AC, Tollervey D. A transcriptome-wide atlas of RNP composition reveals diverse classes of mRNAs and lncRNAs. Cell. 2013;154(5):996–1009. doi:10.1016/j.cell.2013.07.047.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136(4):629–41. doi:10.1016/j.cell.2009.02.006.

    CAS  PubMed  Google Scholar 

  18. Gutschner T, Diederichs S. The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol. 2012;9(6):703–19. doi:10.4161/rna.20481.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009;458(7235):223–7. doi:10.1038/nature07672.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Mercer TR, Dinger ME, Sunkin SM, Mehler MF, Mattick JS. Specific expression of long noncoding RNAs in the mouse brain. Proc Natl Acad Sci U S A. 2008;105(2):716–21. doi:10.1073/pnas.0706729105.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Ravasi T, Suzuki H, Pang KC, Katayama S, Furuno M, Okunishi R, et al. Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome. Genome Res. 2006;16(1):11–9. doi:10.1101/gr.4200206.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Moran VA, Perera RJ, Khalil AM. Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs. Nucleic Acids Res. 2012;40(14):6391–400. doi:10.1093/nar/gks296.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science (New York, NY). 2008;322(5902):750–6. doi:10.1126/science.1163045.

    CAS  Google Scholar 

  24. Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science (New York, NY). 2010;329(5992):689–93. doi:10.1126/science.1192002.

    CAS  Google Scholar 

  25. Ambros V. The functions of animal microRNAs. Nature. 2004;431(7006):350–5. doi:10.1038/nature02871.

    CAS  PubMed  Google Scholar 

  26. Reinhart BJ, Weinstein EG, Rhoades MW, Bartel B, Bartel DP. MicroRNAs in plants. Genes Dev. 2002;16(13):1616–26. doi:10.1101/gad.1004402.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Alvarez-Garcia I, Miska EA. MicroRNA functions in animal development and human disease. Development (Cambridge, England). 2005;132(21):4653–62. doi:10.1242/dev.02073.

    CAS  Google Scholar 

  28. Miska EA. How microRNAs control cell division, differentiation and death. Curr Opin Genet Dev. 2005;15(5):563–8. doi:10.1016/j.gde.2005.08.005.

    CAS  PubMed  Google Scholar 

  29. Baehrecke EH. miRNAs: micro managers of programmed cell death. Curr Biol : CB. 2003;13(12):R473–5.

    CAS  PubMed  Google Scholar 

  30. Fuchs Y, Steller H. Programmed cell death in animal development and disease. Cell. 2011;147(4):742–58. doi:10.1016/j.cell.2011.10.033.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Caldas C, Brenton JD. Sizing up miRNAs as cancer genes. Nat Med. 2005;11(7):712–4. doi:10.1038/nm0705-712.

    CAS  PubMed  Google Scholar 

  32. Shenouda SK, Alahari SK. MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev. 2009;28(3–4):369–78. doi:10.1007/s10555-009-9188-5.

    CAS  PubMed  Google Scholar 

  33. Chen CZ, Li L, Lodish HF, Bartel DP. MicroRNAs modulate hematopoietic lineage differentiation. Science (New York, NY). 2004;303(5654):83–6. doi:10.1126/science.1091903.

    CAS  Google Scholar 

  34. Havelange V, Garzon R. MicroRNAs: emerging key regulators of hematopoiesis. Am J Hematol. 2010;85(12):935–42. doi:10.1002/ajh.21863.

    CAS  PubMed  Google Scholar 

  35. Seitz H. Redefining microRNA targets. Curr Biol : CB. 2009;19(10):870–3. doi:10.1016/j.cub.2009.03.059.

    CAS  PubMed  Google Scholar 

  36. Sarver AL, Subramanian S. Competing endogenous RNA database. Bioinformation. 2012;8(15):731–3. doi:10.6026/97320630008731.

    PubMed  PubMed Central  Google Scholar 

  37. Cesana M, Daley GQ. Deciphering the rules of ceRNA networks. Proc Natl Acad Sci U S A. 2013;110(18):7112–3. doi:10.1073/pnas.1305322110.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M, et al. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell. 2011;147(2):358–69. doi:10.1016/j.cell.2011.09.028.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Franco-Zorrilla JM, Valli A, Todesco M, Mateos I, Puga MI, Rubio-Somoza I, et al. Target mimicry provides a new mechanism for regulation of microRNA activity. Nat Genet. 2007;39(8):1033–7. doi:10.1038/ng2079.

    CAS  PubMed  Google Scholar 

  40. Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, Pandolfi PP. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature. 2010;465(7301):1033–8. doi:10.1038/nature09144.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell. 2011;146(3):353–8. doi:10.1016/j.cell.2011.07.014.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Matouk IJ, Abbasi I, Hochberg A, Galun E, Dweik H, Akkawi M. Highly upregulated in liver cancer noncoding RNA is overexpressed in hepatic colorectal metastasis. Eur J Gastroenterol Hepatol. 2009;21(6):688–92.

    CAS  PubMed  Google Scholar 

  43. Panzitt K, Tschernatsch MM, Guelly C, Moustafa T, Stradner M, Strohmaier HM, et al. Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. Gastroenterology. 2007;132(1):330–42. doi:10.1053/j.gastro.2006.08.026.

    CAS  PubMed  Google Scholar 

  44. Wang J, Liu X, Wu H, Ni P, Gu Z, Qiao Y, et al. CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res. 2010;38(16):5366–83. doi:10.1093/nar/gkq285.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Jendrzejewski J, He H, Radomska HS, Li W, Tomsic J, Liyanarachchi S, et al. The polymorphism rs944289 predisposes to papillary thyroid carcinoma through a large intergenic noncoding RNA gene of tumor suppressor type. Proc Natl Acad Sci U S A. 2012;109(22):8646–51. doi:10.1073/pnas.1205654109.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Fan M, Li X, Jiang W, Huang Y, Li J, Wang Z. A long non-coding RNA, PTCSC3, as a tumor suppressor and a target of miRNAs in thyroid cancer cells. Exp Ther Med. 2013;5(4):1143–6. doi:10.3892/etm.2013.933.

    PubMed  PubMed Central  Google Scholar 

  47. Liu Q, Huang J, Zhou N, Zhang Z, Zhang A, Lu Z, et al. LncRNA loc285194 is a p53-regulated tumor suppressor. Nucleic Acids Res. 2013;41(9):4976–87. doi:10.1093/nar/gkt182.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Qi P, Xu MD, Ni SJ, Huang D, Wei P, Tan C, et al. Low expression of LOC285194 is associated with poor prognosis in colorectal cancer. J Transl Med. 2013;11(1):122. doi:10.1186/1479-5876-11-122.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Johnsson P, Ackley A, Vidarsdottir L, Lui WO, Corcoran M, Grander D, et al. A pseudogene long-noncoding-RNA network regulates PTEN transcription and translation in human cells. Nat Struct Mol Biol. 2013;20(4):440–6. doi:10.1038/nsmb.2516.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Poliseno L, Haimovic A, Christos PJ, Vega YSMEC, Shapiro R, Pavlick A, et al. Deletion of PTENP1 pseudogene in human melanoma. J Investig Dermatol. 2011;131(12):2497–500. doi:10.1038/jid.2011.232.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Wang L, Guo ZY, Zhang R, Xin B, Chen R, Zhao J, et al. Pseudogene OCT4-pg4 functions as a natural micro RNA sponge to regulate OCT4 expression by competing for miR-145 in hepatocellular carcinoma. Carcinogenesis. 2013;34(8):1773–81. doi:10.1093/carcin/bgt139.

    CAS  PubMed  Google Scholar 

  52. Ben-Dov C, Hartmann B, Lundgren J, Valcarcel J. Genome-wide analysis of alternative pre-mRNA splicing. J Biol Chem. 2008;283(3):1229–33. doi:10.1074/jbc.R700033200.

    CAS  PubMed  Google Scholar 

  53. Blencowe BJ. Alternative splicing: new insights from global analyses. Cell. 2006;126(1):37–47. doi:10.1016/j.cell.2006.06.023.

    CAS  PubMed  Google Scholar 

  54. Matlin AJ, Clark F, Smith CW. Understanding alternative splicing: towards a cellular code. Nat Rev Mol Cell Biol. 2005;6(5):386–98. doi:10.1038/nrm1645.

    CAS  PubMed  Google Scholar 

  55. Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet. 2008;40(12):1413–5. doi:10.1038/ng.259.

    CAS  PubMed  Google Scholar 

  56. Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L, Mayr C, et al. Alternative isoform regulation in human tissue transcriptomes. Nature. 2008;456(7221):470–6. doi:10.1038/nature07509.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Long JC, Caceres JF. The SR protein family of splicing factors: master regulators of gene expression. Biochem J. 2009;417(1):15–27. doi:10.1042/bj20081501.

    CAS  PubMed  Google Scholar 

  58. Luco RF, Misteli T. More than a splicing code: integrating the role of RNA, chromatin and non-coding RNA in alternative splicing regulation. Curr Opin Genet Dev. 2011;21(4):366–72. doi:10.1016/j.gde.2011.03.004.

    CAS  PubMed  Google Scholar 

  59. Bernard D, Prasanth KV, Tripathi V, Colasse S, Nakamura T, Xuan Z, et al. A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression. EMBO J. 2010;29(18):3082–93. doi:10.1038/emboj.2010.199.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Ji P, Diederichs S, Wang W, Boing S, Metzger R, Schneider PM, et al. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene. 2003;22(39):8031–41. doi:10.1038/sj.onc.1206928.

    PubMed  Google Scholar 

  61. Tripathi V, Ellis JD, Shen Z, Song DY, Pan Q, Watt AT, et al. The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell. 2010;39(6):925–38. doi:10.1016/j.molcel.2010.08.011.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Lin R, Roychowdhury-Saha M, Black C, Watt AT, Marcusson EG, Freier SM, et al. Control of RNA processing by a large non-coding RNA over-expressed in carcinomas. FEBS Lett. 2011;585(4):671–6. doi:10.1016/j.febslet.2011.01.030.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Tano K, Mizuno R, Okada T, Rakwal R, Shibato J, Masuo Y, et al. MALAT-1 enhances cell motility of lung adenocarcinoma cells by influencing the expression of motility-related genes. FEBS Lett. 2010;584(22):4575–80. doi:10.1016/j.febslet.2010.10.008.

    CAS  PubMed  Google Scholar 

  64. Anko ML, Muller-McNicoll M, Brandl H, Curk T, Gorup C, Henry I, et al. The RNA-binding landscapes of two SR proteins reveal unique functions and binding to diverse RNA classes. Genome Biol. 2012;13(3):R17. doi:10.1186/gb-2012-13-3-r17.

    PubMed  PubMed Central  Google Scholar 

  65. Polymenidou M, Lagier-Tourenne C, Hutt KR, Huelga SC, Moran J, Liang TY, et al. Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43. Nat Neurosci. 2011;14(4):459–68. doi:10.1038/nn.2779.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Sanford JR, Wang X, Mort M, Vanduyn N, Cooper DN, Mooney SD, et al. Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts. Genome Res. 2009;19(3):381–94. doi:10.1101/gr.082503.108.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Schor IE, Lleres D, Risso GJ, Pawellek A, Ule J, Lamond AI, et al. Perturbation of chromatin structure globally affects localization and recruitment of splicing factors. PLoS One. 2012;7(11):e48084. doi:10.1371/journal.pone.0048084.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Tollervey JR, Curk T, Rogelj B, Briese M, Cereda M, Kayikci M, et al. Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Nat Neurosci. 2011;14(4):452–8. doi:10.1038/nn.2778.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Lin R, Maeda S, Liu C, Karin M, Edgington TS. A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas. Oncogene. 2007;26(6):851–8. doi:10.1038/sj.onc.1209846.

    CAS  PubMed  Google Scholar 

  70. Perez DS, Hoage TR, Pritchett JR, Ducharme-Smith AL, Halling ML, Ganapathiraju SC, et al. Long, abundantly expressed non-coding transcripts are altered in cancer. Hum Mol Genet. 2008;17(5):642–55. doi:10.1093/hmg/ddm336.

    CAS  PubMed  Google Scholar 

  71. Yamada K, Kano J, Tsunoda H, Yoshikawa H, Okubo C, Ishiyama T, et al. Phenotypic characterization of endometrial stromal sarcoma of the uterus. Cancer Sci. 2006;97(2):106–12. doi:10.1111/j.1349-7006.2006.00147.x.

    CAS  PubMed  Google Scholar 

  72. Schmidt LH, Spieker T, Koschmieder S, Schaffers S, Humberg J, Jungen D, et al. The long noncoding MALAT-1 RNA indicates a poor prognosis in non-small cell lung cancer and induces migration and tumor growth. J Thorac Oncol : Off Publ Int Assoc Study Lung Cancer. 2011;6(12):1984–92. doi:10.1097/JTO.0b013e3182307eac.

    Google Scholar 

  73. Tripathi V, Shen Z, Chakraborty A, Giri S, Freier SM, Wu X, et al. Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB. PLoS Genet. 2013;9(3):e1003368. doi:10.1371/journal.pgen.1003368.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Lavorgna G, Dahary D, Lehner B, Sorek R, Sanderson CM, Casari G. In search of antisense. Trends Biochem Sci. 2004;29(2):88–94. doi:10.1016/j.tibs.2003.12.002.

    CAS  PubMed  Google Scholar 

  75. Li K, Ramchandran R. Natural antisense transcript: a concomitant engagement with protein-coding transcript. Oncotarget. 2010;1(6):447–52.

    PubMed  PubMed Central  Google Scholar 

  76. Ling MH, Ban Y, Wen H, Wang SM, Ge SX. Conserved expression of natural antisense transcripts in mammals. BMC Genomics. 2013;14:243. doi:10.1186/1471-2164-14-243.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Werner A. Biological functions of natural antisense transcripts. BMC Biol. 2013;11:31. doi:10.1186/1741-7007-11-31.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Beltran M, Puig I, Pena C, Garcia JM, Alvarez AB, Pena R, et al. A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition. Genes Dev. 2008;22(6):756–69. doi:10.1101/gad.455708.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Bertozzi D, Iurlaro R, Sordet O, Marinello J, Zaffaroni N, Capranico G. Characterization of novel antisense HIF-1alpha transcripts in human cancers. Cell Cycle (Georgetown, Tex). 2011;10(18):3189–97.

    CAS  Google Scholar 

  80. Cayre A, Rossignol F, Clottes E, Penault-Llorca F. aHIF but not HIF-1alpha transcript is a poor prognostic marker in human breast cancer. Breast Cancer Res : BCR. 2003;5(6):R223–30. doi:10.1186/bcr652.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Rossignol F, Vache C, Clottes E. Natural antisense transcripts of hypoxia-inducible factor 1alpha are detected in different normal and tumour human tissues. Gene. 2002;299(1–2):135–40.

    CAS  PubMed  Google Scholar 

  82. Fornace Jr AJ, Alamo Jr I, Hollander MC. DNA damage-inducible transcripts in mammalian cells. Proc Natl Acad Sci U S A. 1988;85(23):8800–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Hollander MC, Alamo I, Fornace Jr AJ. A novel DNA damage-inducible transcript, gadd7, inhibits cell growth, but lacks a protein product. Nucleic Acids Res. 1996;24(9):1589–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Jackman J, Alamo Jr I, Fornace Jr AJ. Genotoxic stress confers preferential and coordinate messenger RNA stability on the five gadd genes. Cancer Res. 1994;54(21):5656–62.

    CAS  PubMed  Google Scholar 

  85. Liu X, Li D, Zhang W, Guo M, Zhan Q. Long non-coding RNA gadd7 interacts with TDP-43 and regulates Cdk6 mRNA decay. EMBO J. 2012;31(23):4415–27. doi:10.1038/emboj.2012.292.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Kim YK, Furic L, Desgroseillers L, Maquat LE. Mammalian Staufen1 recruits Upf1 to specific mRNA 3′UTRs so as to elicit mRNA decay. Cell. 2005;120(2):195–208. doi:10.1016/j.cell.2004.11.050.

    CAS  PubMed  Google Scholar 

  87. Kim YK, Furic L, Parisien M, Major F, DesGroseillers L, Maquat LE. Staufen1 regulates diverse classes of mammalian transcripts. EMBO J. 2007;26(11):2670–81. doi:10.1038/sj.emboj.7601712.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Gong C, Maquat LE. lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3′ UTRs via Alu elements. Nature. 2011;470(7333):284–8. doi:10.1038/nature09701.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Gong C, Maquat LE. “Alu” strious long ncRNAs and their role in shortening mRNA half-lives. Cell Cycle (Georgetown, Tex). 2011;10(12):1882–3.

    CAS  Google Scholar 

  90. Kretz M, Siprashvili Z, Chu C, Webster DE, Zehnder A, Qu K, et al. Control of somatic tissue differentiation by the long non-coding RNA TINCR. Nature. 2013;493(7431):231–5. doi:10.1038/nature11661.

    CAS  PubMed  Google Scholar 

  91. Roy B, Jacobson A. The intimate relationships of mRNA decay and translation. Trends Genet : TIG. 2013;29(12):691–9. doi:10.1016/j.tig.2013.09.002.

    CAS  PubMed  Google Scholar 

  92. Aktas BH, Qiao Y, Ozdelen E, Schubert R, Sevinc S, Harbinski F, et al. Small-molecule targeting of translation initiation for cancer therapy. Oncotarget. 2013;4(10):1606–17.

    PubMed  PubMed Central  Google Scholar 

  93. Cohen N, Sharma M, Kentsis A, Perez JM, Strudwick S, Borden KL. PML RING suppresses oncogenic transformation by reducing the affinity of eIF4E for mRNA. EMBO J. 2001;20(16):4547–59. doi:10.1093/emboj/20.16.4547.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. De Benedetti A, Graff JR. eIF-4E expression and its role in malignancies and metastases. Oncogene. 2004;23(18):3189–99. doi:10.1038/sj.onc.1207545.

    PubMed  Google Scholar 

  95. Graff JR, Zimmer SG. Translational control and metastatic progression: enhanced activity of the mRNA cap-binding protein eIF-4E selectively enhances translation of metastasis-related mRNAs. Clin Exp Metastasis. 2003;20(3):265–73.

    CAS  PubMed  Google Scholar 

  96. Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 2010;142(3):409–19. doi:10.1016/j.cell.2010.06.040.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Yoon JH, Abdelmohsen K, Srikantan S, Yang X, Martindale JL, De S, et al. LincRNA-p21 suppresses target mRNA translation. Mol Cell. 2012;47(4):648–55. doi:10.1016/j.molcel.2012.06.027.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Wilusz CJ, Wilusz J. HuR and translation—the missing linc(RNA). Mol Cell. 2012;47(4):495–6. doi:10.1016/j.molcel.2012.08.005.

    CAS  PubMed  Google Scholar 

  99. Carrieri C, Cimatti L, Biagioli M, Beugnet A, Zucchelli S, Fedele S, et al. Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat. Nature. 2012;491(7424):454–7. doi:10.1038/nature11508.

    CAS  PubMed  Google Scholar 

  100. Huarte M. LncRNAs have a say in protein translation. Cell Res. 2013;23(4):449–51. doi:10.1038/cr.2012.169.

    CAS  PubMed  Google Scholar 

  101. Orom UA, Derrien T, Beringer M, Gumireddy K, Gardini A, Bussotti G, et al. Long noncoding RNAs with enhancer-like function in human cells. Cell. 2010;143(1):46–58. doi:10.1016/j.cell.2010.09.001.

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Gumireddy K, Li A, Yan J, Setoyama T, Johannes GJ, Orom UA, et al. Identification of a long non-coding RNA-associated RNP complex regulating metastasis at the translational step. EMBO J. 2013;32(20):2672–84. doi:10.1038/emboj.2013.188.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Wapinski O, Chang HY. Long noncoding RNAs and human disease. Trends Cell Biol. 2011;21(6):354–61. doi:10.1016/j.tcb.2011.04.001.

    CAS  PubMed  Google Scholar 

  104. Yang F, Huo XS, Yuan SX, Zhang L, Zhou WP, Wang F, et al. Repression of the long noncoding RNA-LET by histone deacetylase 3 contributes to hypoxia-mediated metastasis. Mol Cell. 2013;49(6):1083–96. doi:10.1016/j.molcel.2013.01.010.

    CAS  PubMed  Google Scholar 

  105. Guo F, Li Y, Liu Y, Wang J, Li G. Inhibition of metastasis-associated lung adenocarcinoma transcript 1 in CaSki human cervical cancer cells suppresses cell proliferation and invasion. Acta Biochim Biophys Sin. 2010;42(3):224–9.

    CAS  PubMed  Google Scholar 

  106. Zhai H, Fesler A, Schee K, Fodstad O, Flatmark K, Ju J. Clinical significance of long intergenic noncoding RNA-p21 in colorectal cancer. Clin Colorectal Cancer. 2013;12(4):261–6. doi:10.1016/j.clcc.2013.06.003.

    CAS  PubMed  Google Scholar 

  107. Keniry A, Oxley D, Monnier P, Kyba M, Dandolo L, Smits G, et al. The H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and Igf1r. Nat Cell Biol. 2012;14(7):659–65. doi:10.1038/ncb2521.

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 81170064) and the Natural Science Foundation of China (No. 81302032). We apologize to all researchers whose relevant contributions were not cited due to space limitations.

Authors’ contributions

YS conceived of the review and participated in its design. XFS and MS drafted the manuscript. YW drafted Table 1. LW and YWY drafted the figures and the figure legends. HBL, DMY, and CHL participated in the design of the study and helped to draft the manuscript. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, China

    Xuefei Shi, Ying Wu, Yanwen Yao, Hongbing Liu, Guannan Wu, Dongmei Yuan & Yong Song

  2. Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China

    Ming Sun

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  1. Xuefei Shi
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  2. Ming Sun
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Correspondence to Yong Song.

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Xuefei Shi and Ming Sun contributed equally to the work and should be regarded as joint first authors.

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Shi, X., Sun, M., Wu, Y. et al. Post-transcriptional regulation of long noncoding RNAs in cancer. Tumor Biol. 36, 503–513 (2015). https://doi.org/10.1007/s13277-015-3106-y

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