Molecular function and regulation of long non-coding RNAs: paradigms with potential roles in cancer

Tumor Biology

Volumn 35, Issue 11, 2014, Pages 10645-10663

  Hajjari, Mohammadreza ^a   Khoshnevisan, Atefeh ^b   Shin, Young Kee ^b,c  

^a SHAHID CHAMRAN UNIVERSITY OF AHVAZ   (Iran)

^b Seoul National University   (South Korea)

^c Seoul National University   (South Korea)

Author keywords

Cancer; LncRNAs; Oncogenes; Tumor suppressor genes

Indexed keywords

ANRIL PROTEIN; BIOLOGICAL MARKER; CELL CYCLE PROTEIN; CYCLIN DEPENDENT KINASE INHIBITOR; DNA METHYLTRANSFERASE; GROWTH ARREST SPECIFIC TRANSCRIPT 5; HOX ANTISENSE INTERGENIC RNA; HULC PROTEIN; HYPOXIA INDUCIBLE FACTOR 1ALPHA; LONG UNTRANSLATED RNA; MATERNALLY EXPRESSED GENE 3; METASTASIS ASSOCIATED LUNG ADENOCARCINOMA TRANSCRIPT 1; POLYCOMB GROUP PROTEIN; PROTEIN P53; REGULATOR PROTEIN; RNA; RNA H19; SCAFFOLD PROTEIN; STAT1 PROTEIN; STEROID RECEPTOR RNA ACTIVATOR; TAURINE UPREGULATED GENE 1; TELOMERASE; TELOMERE BINDING PROTEIN; TELOMERIC REPEAT CONTAINING RNA; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR ETS 2; TUMOR SUPPRESSOR PROTEIN; UNCLASSIFIED DRUG; UNTRANSLATED RNA; UPSTREAM STIMULATORY FACTOR; UROTHELIAL CARCINOMA ASSOCIATED 1;

CANCER GROWTH; EPIGENETICS; GENE; GENE EXPRESSION REGULATION; GENE FUNCTION; GENE INTERACTION; GENE LOCUS; GENETIC REGULATION; HUMAN; MALIGNANT NEOPLASTIC DISEASE; NONHUMAN; NUCLEOTIDE BINDING SITE; ONCOGENE; PANDA GENE; PCA3 GENE; PCAT 1 GENE; PCGEM1 GENE; PRIORITY JOURNAL; PRNCR1 GENE; PROMOTER REGION; PROSTATE CANCER; PROTEIN TARGETING; REVIEW; SIGNAL TRANSDUCTION; UPREGULATION; ANIMAL; GENETICS; STOMACH NEOPLASMS;

ANIMALS; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; RNA, LONG NONCODING; SIGNAL TRANSDUCTION; STOMACH NEOPLASMS;

EID: 84921937504     PISSN: 10104283     EISSN: 14230380     Source Type: Journal    
DOI: 10.1007/s13277-014-2636-z     Document Type: Review

References (201)

1. Esteller M. Non-coding RNAs in human disease. Nat Rev Genet. 2011;12(12):861–74.
2. Wu Q, Kim YC, Lu J, Xuan Z, Chen J, Zheng Y, et al. Poly A- transcripts expressed in HeLa cells. PLoS One. 2008;3(7):e2803.
3. Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10:155–9.
4. Brown CJ, Hendrich BD, Rupert JL, Lafrenière RG, Xing Y, Lawrence J, et al. The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell. 1992;71(3):527–42.
5. Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science. 2008;322(5902):750–6.
6. Jeon Y, Lee JT. YY1 tethers Xist RNA to the inactive X nucleation center. Cell. 2011;146(1):119–33.
7. Hajjari M, Behmanesh M, Jahani M. In silico finding of putative cis-acting elements for the tethering of polycomb repressive complex2 in human genome. Bioinformation. 2014;10(4):187–90.
8. Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136:629–41.
9. Wilusz JE, Sunwoo H, Spector DL. Long noncoding RNAs: functional surprises from the RNA world. Genes Dev. 2009;23:1494–504.
10. Bernstein E, Allis CD. RNA meets chromatin. Genes Dev. 2005;19:1635–55.
11. Whitehead J, Pandey GK, Kanduri C. Regulation of the mammalian epigenome by long noncoding RNAs. Biochim Biophys Acta. 2009;1790:936–47.
12. Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011;43:904–14.
13. Clark MB, Mattick JS. Long noncoding RNAs in cell biology. Semin Cell Dev Biol. 2011;22:366–76.
14. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144. doi:10.1016/j.cell.2011.02.013.
15. Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071–6.
16. Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell. 2007;129:1311–23.
17. Yang Z, Zhou L, Wu LM, Lai MC, Xie HY, Zhang F, et al. Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann Surg Oncol. 2011;18(5):1243–50.
18. Ding C, Cheng S, Yang Z, Lv Z, Xiao H, Du C, et al. Long non-coding RNA HOTAIR promotes cell migration and invasion via down-regulation of RNA binding motif protein 38 in hepatocellular carcinoma cells. Int J Mol Sci. 2014;15(3):4060–76.
19. Kogo R, Shimamura T, Mimori K, Kawahara K, Imoto S, Sudo T, et al. Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res. 2011;71(20):6320–6.
20. Niinuma T, Suzuki H, Nojima M, Nosho K, Yamamoto H, Takamaru H, et al. Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors. Cancer Res. 2012;72(5):1126–36.
21. Kim K, Jutooru I, Chadalapaka G, Johnson G, Frank J, Burghardt R, et al. HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene. 2013;32(13):1616–25.
22. Hajjari M, Behmanesh M, Sadeghizadeh M, Zeinoddini M. Up-regulation of HOTAIR long non-coding RNA in human gastric adenocarcinoma tissues. Med Oncol. 2013;30(3):670.
23. Liu XH, Liu ZL, Sun M, Liu J, Wang ZX, De W. The long non-coding RNA HOTAIR indicates a poor prognosis and promotes metastasis in non-small cell lung cancer. BMC Cancer. 2013;13:464.
24. Zhang JX, Han L, Bao ZS, Wang YY, Chen LY, Yan W, et al. HOTAIR, a cell cycle-associated long noncoding RNA and a strong predictor of survival, is preferentially expressed in classical and mesenchymal glioma. Neuro Oncol. 2013;15(12):1595–603.
25. Qiu JJ, Lin YY, Ye LC, Ding JX, Feng WW, Jin HY, et al. Overexpression of long non-coding RNA HOTAIR predicts poor patient prognosis and promotes tumor metastasis in epithelial ovarian cancer. Gynecol Oncol. 2014.
26. Lu L, Zhu G, Zhang C, Deng Q, Katsaros D, Mayne ST, et al. Association of large noncoding RNA HOTAIR expression and its downstream intergenic CpG island methylation with survival in breast cancer. Breast Cancer Res Treat. 2012;136(3):875–83.
27. Ge XS, Ma HJ, Zheng XH, Ruan HL, Liao XY, Xue WQ, et al. HOTAIR, a prognostic factor in esophageal squamous cell carcinoma, inhibits WIF-1 expression and activates Wnt pathway. Cancer Sci. 2013;104(12):1675–82.
28. Wang L, Zeng X, Chen S, Ding L, Zhong J, Zhao JC, et al. BRCA1 is a negative modulator of the PRC2 complex. EMBO J. 2013;32(11):1584–97.
29. 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. 329(5992):689–93.
30. Amort T, Soulière MF, Wille A, Jia XY, Fiegl H, Wörle H, et al. Long non-coding RNAs as targets for cytosine methylation. RNA Biol. 2013;10(6).
31. Liu XH, Sun M, Nie FQ, Ge YB, Zhang EB, Yin DD, et al. Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer. 2014;13(1):92.
32. Zhuang Y, Wang X, Nguyen HT, Zhuo Y, Cui X, Fewell C, et al. Induction of long intergenic non-coding RNA HOTAIR in lung cancer cells by type I collagen. J Hematol Oncol. 2013;6(35): doi:10.1186/756-8722-6-35.
33. Bhan A, Hussain I, Ansari KI, Kasiri S, Bashyal A, Mandal SS. Antisense Transcript Long Noncoding RNA (lncRNA) HOTAIR is Transcriptionally Induced by Estradiol. J Mol Biol. 2013;S0022-2836(13):00038-7.
34. Pádua Alves C, Fonseca AS, Muys BR, de Barros E, Lima Bueno R, Bürger MC, et al. Brief report: the lincRNA Hotair is required for epithelial-to-mesenchymal transition and stemness maintenance of cancer cell lines. Stem Cells. 2013;31(12):2827–32.
35. Chiyomaru T, Fukuhara S, Saini S, Majid S, Deng G, Shahryari V, et al. Long Non-coding RNA HOTAIR Is Targeted and Regulated by miR-141 in Human Cancer Cells. J Biol Chem. 2014;289(18).
36. Xu ZY, Yu QM, Du YA, Yang LT, Dong RZ, Huang L, et al. Knockdown of long non-coding RNA HOTAIR suppresses tumor invasion and reverses epithelial-mesenchymal transition in gastric cancer. Int J Biol Sci. 2013;9(6):587–97.
37. Carrion K, Dyo J, Patel V, Sasik R, Mohamed SA, Hardiman G, et al. The long non-coding HOTAIR is modulated by cyclic stretch and WNT/β-CATENIN in human aortic valve cells and is a novel repressor of calcification genes. PLoS One. 2014;9(5):e96577.
38. Endo H, Shiroki T, Nakagawa T, Yokoyama M, Tamai K, Yamanami H, et al. Enhanced expression of long non-coding RNA HOTAIR is associated with the development of gastric cancer. PLoS One. 2013;8(10):e77070.
39. Hajjari M, Khoshnevisan A. Potential long non-coding RNAs to be considered as biomarkers or therapeutic targets in gastric cancer. Front Genet. 2013;4:210.
40. Cai B, Song XQ, Cai JP, Zhang S. HOTAIR: a cancer-related long non-coding RNA. Neoplasma. 2014;61(4):379–91.
41. Zhang X, Zhou L, Fu G, Sun F, Shi J, Wei J, et al. The identification of a ESCC susceptibility SNP rs920778 that regulates the expression of lncRNA HOTAIR via a novel intronic enhancer. Carcinogenesis. 2014;35(9):2062–7.
42. Ji P, Diederichs S, Wang W, Böing 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.
43. Xu C, Yang M, Tian J, Wang X, Li Z. MALAT-1: a long non-coding RNA and its important 3' end functional motif in colorectal cancer metastasis. Int J Oncol. 2011;39(1):169–75.
44. 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.
45. Fan Y, Shen B, Tan M, Mu X, Qin Y, Zhang F, et al. TGF-β-induced upregulation of malat1 promotes bladder cancer metastasis by associating with suz12. Clin Cancer Res. 2014;20(6):1531–41.
46. Wu XS, Wang XA, Wu WG, Hu YP, Li ML, Ding Q, et al. MALAT1 promotes the proliferation and metastasis of gallbladder cancer cells by activating the ERK/MAPK pathway. Cancer Biol Ther. 2014;15(6):806–14.
47. Ren S, Liu Y, Xu W, Sun Y, Lu J, Wang F, et al. Long noncoding RNA MALAT-1 is a new potential therapeutic target for castration resistant prostate cancer. J Urol. 2013;190(6):2278–87.
48. Lai MC, Yang Z, Zhou L, Zhu QQ, Xie HY, Zhang F, et al. Long non-coding RNA MALAT-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation. Med Oncol. 2012;29(3):1810–6.
49. Rajaram V, Knezevich S, Bove KE, Perry A, Pfeifer JD. DNA sequence of the translocation breakpoints in undifferentiated embryonal sarcoma arising in mesenchymal hamartoma of the liver harboring the t(11;19)(q11;q13.4) translocation. Genes Chromosom Cancer. 2007;46(5):508–13.
50. 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.
51. Wang J, Su L, Chen X, Li P, Cai Q, Yu B, et al. MALAT1 promotes cell proliferation in gastric cancer by recruiting SF2/ASF. Biomed Pharmacother. 2014.
52. Gutschner T, Hämmerle M, Eissmann M, Hsu JKY, Hung G, Revenko A, et al. The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res. 2013;73(3):1180–9.
53. 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.
54. Yang L, Lin C, Liu W, Zhang J, Ohgi KA, Grinstein JD, et al. ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. Cell. 2011;147(4):773–88.
55. 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.
56. Yang F, Yi F, Han X, Du Q, Liang Z. MALAT-1 interacts with hnRNP C in cell cycle regulation. FEBS Lett. 2013;587(19):3175–81.
57. Eißmann M, Gutschner T, Hämmerle M, Günther S, Caudron-Herger M, Groß M, et al. Loss of the abundant nuclear non-coding RNA MALAT1 is compatible with life and development. RNA Biol. 2012;9(8):1076–87.
58. Ying L, Chen Q, Wang Y, Zhou Z, Huang Y, Qiu F. Upregulated MALAT-1 contributes to bladder cancer cell migration by inducing epithelial-to-mesenchymal transition. Mol Biosyst. 2012;8(9):2289–94.
59. Wilusz JE, Freier SM, Spector DL. Long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA. Cell. 2008;135:919–32.
60. Wilusz JE, Jnbaptiste CK, Lu LY, Kuhn CD, Joshua-Tor L, Sharp PA. A triple helix stabilizes the 3′ ends of long noncoding RNAs that lack poly(A) tails. Genes Dev. 2012;26:2392–407.
61. Wang J, Wang H, Zhang Y, Zhen N, Zhang L, Qiao Y, et al. Mutual inhibition between YAP and SRSF1 maintains long non-coding RNA, Malat1-induced tumourigenesis in liver cancer. Cell Signal. 2014;26(5):1048–59.
62. Han Y, Liu Y, Zhang H, Wang T, Diao R, Jiang Z, et al. Hsa-miR-125b suppresses bladder cancer development by down-regulating oncogene SIRT7 and oncogenic long non-coding RNA MALAT1. FEBS Lett. 2013;587(23):3875–82.
63. Leucci E, Patella F, Waage J, Holmstrøm K, Lindow M, Porse B, et al. microRNA-9 targets the long non-coding RNA MALAT1 for degradation in the nucleus. Sci Rep. 2013;3:2535.
64. Tee AE, Ling D, Nelson C, Atmadibrata B, Dinger ME, Xu N, et al. The histone demethylase JMJD1A induces cell migration and invasion by up-regulating the expression of the long noncoding RNA MALAT1. Oncotarget. 2014;5(7):1793–804.
65. Koshimizu TA, Fujiwara Y, Sakai N, Shibata K, Tsuchiya H. Oxytocin stimulates expression of a noncoding RNA tumor marker in a human neuroblastoma cell line. Life Sci. 2010;86(11–12):1455–60.
66. Weber DG, Johnen G, Casjens S, Bryk O, Pesch B, Jöckel KH, et al. Evaluation of long noncoding RNA MALAT1 as a candidate blood-based biomarker for the diagnosis of non-small cell lung cancer. BMC Res Notes. 2013;6(518).
67. Lanz RB, McKenna NJ, Onate SA, Albrecht U, Wong J, Tsai SY, et al. A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Cell Signal. 1999;97(1):17–27.
68. Hubé F, Velasco G, Rollin J, Furling D, Francastel C. Steroid receptor RNA activator protein binds to and counteracts SRA RNA-mediated activation of MyoD and muscle differentiation. Nucleic Acids Res. 2011;39(2):513–25.
69. Colley SM, Leedman PJ. Steroid Receptor RNA Activator - A nuclear receptor coregulator with multiple partners: Insights and challenges. Biochimie. 2011;93(11):1966–72.
70. Leygue E, Dotzlaw H, Watson PH, Murphy LC. Expression of the steroid receptor RNA activator in human breast tumors. Cancer Res. 1999;59(17):4190–3.
71. Hatchell EC, Colley SM, Beveridge DJ, Epis MR, Stuart LM, Giles KM, et al. SLIRP, a small SRA binding protein, is a nuclear receptor corepressor. Mol Cell. 2006;22(5):657–68.
72. Shi Y, Downes M, Xie W, Kao HY, Ordentlich P, Tsai CC, et al. Sharp, an inducible cofactor that integrates nuclear receptor repression and activation. Genes Dev. 2001;15(9):1140–51.
73. Xu B, Yang WH, Gerin I, Hu CD, Hammer GD, Koenig RJ. Dax-1 and steroid receptor RNA activator (SRA) function as transcriptional coactivators for steroidogenic factor 1 in steroidogenesis. Mol Cell Biol. 2009;29(7):1719–34.
74. Brent GA. The molecular basis of thyroid hormone action. N Engl J Med. 1994;331:847–53.
75. Redfern AD, Colley SM, Beveridge DJ, Ikeda N, Epis MR, Li X, et al. RNA-induced silencing complex (RISC) Proteins PACT, TRBP, and Dicer are SRA binding nuclear receptor coregulators. Proc Natl Acad Sci U S A. 2013;110(16):6536–41.
76. Jung C, Mittler G, Oswald F, Borggrefe T. RNA helicase Ddx5 and the noncoding RNA SRA act as coactivators in the Notch signaling pathway. Biochim Biophys Acta. 2013;1833(5):1180–9.
77. Xu B, Gerin I, Miao H, Vu-Phan D, Johnson CN, Xu R, et al. Multiple roles for the non-coding RNA SRA in regulation of adipogenesis and insulin sensitivity. PLoS One. 2010;5(12):e14199.
78. Liu S, Xu R, Gerin I, Cawthorn WP, Macdougald OA, Chen XW, et al. SRA regulates adipogenesis by modulating p38/JNK phosphorylation and stimulating insulin receptor gene expression and downstream signaling. PLoS One. 2014;9(4).
79. Beato M, Vicent GP. A new role for an old player: steroid receptor RNA Activator (SRA) represses hormone inducible genes. Transcription. 2013;4(4):pii: 25777.
80. Zhao X, Patton JR, Ghosh SK, Fischel-Ghodsian N, Shen L, Spanjaard RA. Pus3p- and Pus1p-dependent pseudouridylation of steroid receptor RNA activator controls a functional switch that regulates nuclear receptor signaling. Mol Endocrinol. 2007;21(3):686–99.
81. 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.
82. Xie H, Ma H, Zhou D. Plasma HULC as a promising novel biomarker for the detection of hepatocellular carcinoma. Biomed Res Int. 2013;2013:136106.
83. Zhao Y, Guo Q, Chen J, Hu J, Wang S, Sun Y. Role of long non-coding RNA HULC in cell proliferation, apoptosis and tumor metastasis of gastric cancer: a clinical and in vitro investigation. Oncol Rep. 2014;31(1):358–64.
84. 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.
85. 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.
86. Hämmerle M, Gutschner T, Uckelmann H, Ozgur S, Fiskin E, Groß M, et al. Post-transcriptional destabilization of the liver-specific long non-coding RNA HULC by the IGF2 mRNA-binding protein 1 (IGF2BP1). Hepatology. 2013;58(5):1703–12.
87. Doidge R, Mittal S, Aslam A, Winkler GS. Deadenylation of cytoplasmic mRNA by the mammalian Ccr4-Not complex. Biochem Soc Trans. 2012;40:96–901.
88. Pasmant E, Laurendeau I, Heron D, Vidaud M, Vidaud D, Bieche I. Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: identification of ANRIL, an antisense noncoding RNA whose expression coclusters with ARF. Cancer Res. 2007;67(8):3963–9.
89. Yu W, Gius D, Onyango P, Muldoon-Jacobs K, Karp J, Feinberg AP, et al. Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature. 2008;451(7175):202–6.
90. Folkersen L, Kyriakou T, Goel A, Peden J, Mälarstig A, Paulsson-Berne G, et al. Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants. PLoS One. 2009;4(11):e7677.
91. Cunnington MS, Santibanez Koref M, Mayosi BM, Burn J, Keavney B. Chromosome 9p21 SNPs associated with multiple disease phenotypes correlate with ANRIL expression. PLoS Genet. 2010;6(4):e1000899.
92. Iacobucci I, Sazzini M, Garagnani P, Ferrari A, Boattini A, Lonetti A, et al. A polymorphism in the chromosome 9p21 ANRIL locus is associated to Philadelphia positive acute lymphoblastic leukemia. Leuk Res. 2011;35(8):1052–9.
93. Kitagawa M, Kotake Y, Ohhata T. Long non-coding RNAs involved in cancer development and cell fate determination. Curr Drug Targets. 2012;13(13):1616–21.
94. Kotake Y, Nakagawa T, Kitagawa K, Suzuki S, Liu N, Kitagawa M, et al. Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene. Oncogene. 2011;30(16):1956–62.
95. Yap KL, Li S, Muñoz-Cabello AM, Raguz S, Zeng L, Mujtaba S, et al. Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell. 2010;38(5):662–74.
96. Chen D, Zhang Z, Mao C, Zhou Y, Yu L, Yin Y, et al. ANRIL inhibits p15INK4b through the TGFβ1 signaling pathway in human esophageal squamous cell carcinoma. Cell Immunol. 2014;289(1–2):9106.
97. Ghosh AK, Varga J. The transcriptional coactivator and acetyltransferase p300 in fibroblast biology and fibrosis. J Cell Physiol. 2007;213:663–71.
98. Bochenek G, Häsler R, El Mokthari NE, König IR, Loos BG, Rosenstiel P, et al. The large non-coding RNA ANRIL, which is associated with atherosclerosis, periodontitis, and several forms of cancer, regulates ADIPOR1, VAMP3, and C11ORF10. Hum Mol Genet. 2013;22(22):4516–27.
99. Zhang EB, Kong R, Yin DD, You LH, Sun M, Han L, et al. Long noncoding RNA ANRIL indicates a poor prognosis of gastric cancer and promotes tumor growth by epigenetically silencing of miR-99a/miR-449a. Oncotarget. 2014;5(8):2276–92.
100. Holdt LM, Hoffmann S, Sass K, Langenberger D, Scholz M, Krohn K, et al. Alu elements in ANRIL non-coding RNA at chromosome 9p21 modulate atherogenic cell functions through trans-regulation of gene networks. PLoS Genet. 2013;9(7):e1003588.
101. Wan G, Mathur R, Hu X, Liu Y, Zhang X, Peng G, et al. Long non-coding RNA ANRIL (CDKN2B-AS) is induced by the ATM-E2F1 signaling pathway. Cell Signal. 2013;25(5):1086–95.
102. Harismendy O, Notani D, Song X, Rahim NG, Tanasa B, Heintzman N, et al. 9p21 DNA variants associated with coronary artery disease impair interferon-γ signalling response. Nature. 2011;470(7333):264–8.
103. Schaefer AS, Richter GM, Dommisch H, Reinartz M, Nothnagel M, Noack B, et al. CDKN2BAS is associated with periodontitis in different European populations and is activated by bacterial infection. J Med Genet. 2011;48(1):38–74.
104. Hirosue A, Ishihara K, Tokunaga K, Watanabe T, Saitoh N, Nakamoto M, et al. Quantitative assessment of higher-order chromatin structure of the INK4/ARF locus in human senescent cells. Aging Cell. 2012;11(3):553–6.
105. Wang F, Li X, Xie X, Zhao L, Chen W. UCA1, a non-protein-coding RNA up-regulated in bladder carcinoma and embryo, influencing cell growth and promoting invasion. FEBS Lett. 2008;582(13):1919–27.
106. Liu SP, Yang JX, Cao DY, Shen K. Identification of differentially expressed long non-coding RNAs in human ovarian cancer cells with different metastatic potentials. Cancer Biol Med. 2013;10(3):138–41.
107. Yang C, Li X, Wang Y, Zhao L, Chen W. Long non-coding RNA UCA1 regulated cell cycle distribution via CREB through PI3-K dependent pathway in bladder carcinoma cells. Gene. 2012;496(1):8–16.
108. Fan Y, Shen B, Tan M, Mu X, Qin Y, Zhang F, et al. Long non-coding RNA UCA1 increases chemoresistance of bladder cancer cells by regulating Wnt signaling. FEBS J. 2014;281(7):1750–8.
109. Huang J, Zhou N, Watabe K, Lu Z, Wu F, Xu M, et al. Long non-coding RNA UCA1 promotes breast tumor growth by suppression of p27 (Kip1). Cell Death Dis. 2014;5:e1008.
110. Wu W, Zhang S, Li X, Xue M, Cao S, Chen W. Ets-2 regulates cell apoptosis via the Akt pathway, through the regulation of urothelial cancer associated 1, a long non-coding RNA, in bladder cancer cells. PLoS One. 2013;8(9):e73920.
111. Xue M, Li X, Li Z, Chen W. Urothelial carcinoma associated 1 is a hypoxia-inducible factor-1α-targeted long noncoding RNA that enhances hypoxic bladder cancer cell proliferation, migration, and invasion. Tumour Biol. 2014;35(7):6901–12.
112. Bussemakers MJ, van Bokhoven A, Verhaegh GW, Smit FP, Karthaus HF, Schalken JA, et al. DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res. 1999;59(23):5975–9.
113. Clarke RA, Zhao Z, Guo AY, Roper K, Teng L, Fang ZM, et al. New genomic structure for prostate cancer specific gene PCA3 within BMCC1: implications for prostate cancer detection and progression. PLoS ONE. 2009;4:e4995.
114. de Kok JB, Verhaegh GW, Roelofs RW, Hessels D, Kiemeney LA, Aalders TW, et al. DD3(PCA3), a very sensitive and specific marker to detect prostate tumors. Cancer Res. 2002;62(9):2695–8.
115. Tinzl M, Marberger M, Horvath S, Chypre C. DD3PCA3 RNA analysis in urine–a new perspective for detecting prostate cancer. Eur Urol. 2004;46(2):182–7.
116. Klecka J, Holubec L, Pesta M, Topolcan O, Hora M, Eret V, et al. Differential display code 3 (DD3/PCA3) in prostate cancer diagnosis. Anticancer Res. 2010;30(2):665–70.
117. Ferreira LB, Palumbo A, de Mello KD, Sternberg C, Caetano MS, de Oliveira FL, et al. PCA3 noncoding RNA is involved in the control of prostate-cancer cell survival and modulates androgen receptor signaling. BMC Cancer. 2012;12:507.
118. Prensner JR, Iyer MK, Balbin OA, Dhanasekaran SM, Cao Q, Brenner JC, et al. Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression. Nat Biotechnol. 2011;29(8):742–9.
119. Prensner JR, Chen W, Iyer MK, Cao Q, Ma T, Han S, et al. PCAT-1, a long noncoding RNA, regulates BRCA2 and controls homologous recombination in cancer. Cancer Res. 2014;74(6):1651–60.
120. Ge X, Chen Y, Liao X, Liu D, Li F, Ruan H, et al. Overexpression of long noncoding RNA PCAT-1 is a novel biomarker of poor prognosis in patients with colorectal cancer. Med Oncol. 2013;30(2):588.
121. Srikantan V, Zou Z, Petrovics G, Xu L, Augustus M, Davis L, et al. PCGEM1, a prostate-specific gene, is overexpressed in prostate cancer. Proc Natl Acad Sci U S A. 2000;97(22):12216–21.
122. Petrovics G, Zhang W, Makarem M, Street JP, Connelly R, Sun L, et al. Elevated expression of PCGEM1, a prostate-specific gene with cell growth-promoting function, is associated with high-risk prostate cancer patients. Oncogene. 2004;23(2):605–11.
123. Fu X, Ravindranath L, Tran N, Petrovics G, Srivastava S. Regulation of apoptosis by a prostate-specific and prostate cancer-associated noncoding gene, PCGEM1. DNA Cell Biol. 2006;25(3):135–41.
124. Ifere GO, Barr E, Equan A, Gordon K, Singh UP, Chaudhary J, et al. Differential effects of cholesterol and phytosterols on cell proliferation, apoptosis and expression of a prostate specific gene in prostate cancer cell lines. Cancer Detect Prev. 2009;32(4):319–28.
125. Yang L, Lin C, Jin C, Yang JC, Tanasa B, Li W, et al. lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs. Nature. 2013;500(7464):598–602.
126. Chung S, Nakagawa H, Uemura M, Piao L, Ashikawa K, Hosono N, et al. Association of a novel long non-coding RNA in 8q24 with prostate cancer susceptibility. Cancer Sci. 2011;102(1):245–52.
127. Zhang X, Zhou Y, Mehta KR, Danila DC, Scolavino S, Johnson SR, et al. A pituitary-derived MEG3 isoform functions as a growth suppressor in tumor cells. J Clin Endocrinol Metab. 2003;88(11):5119–26.
128. Benetatos L, Vartholomatos G, Hatzimichael E. MEG3 imprinted gene contribution in tumorigenesis. Int J Cancer. 2011;129(4):773–9.
129. Jia LF, Wei SB, Gan YH, Guo Y, Gong K, Mitchelson K, et al. Expression, regulation and roles of MiR-26a and MEG3 in tongue squamous cell carcinoma. Int J Cancer. 2014;135(10):2282–93.
130. Ying L, Huang Y, Chen H, Wang Y, Xia L, Chen Y, et al. Downregulated MEG3 activates autophagy and increases cell proliferation in bladder cancer. Mol Biosyst. 2013;9(3):407–11.
131. Qin R, Chen Z, Ding Y, Hao J, Hu J, Guo F. Long non-coding RNA MEG3 inhibits the proliferation of cervical carcinoma cells through the induction of cell cycle arrest and apoptosis. Neoplasma. 2013;60(5):486–92.
132. Ribarska T, Goering W, Droop J, Bastian KM, Ingenwerth M, Schulz WA. Deregulation of an imprinted gene network in prostate cancer. Epigenetics. 2014;9(5):704–17.
133. Zhou Y, Zhong Y, Wang Y, Zhang X, Batista DL, Gejman R, et al. Activation of p53 by MEG3 non-coding RNA. J Biol Chem. 2007;282:24731–42.
134. Zhang X, Zhou Y, Klibanski A. Isolation and characterization of novel pituitary tumor related genes: a cDNA representational difference approach. Mol Cell Endocrinol. 2010;326:40–7.
135. Gordon FE, Nutt CL, Cheunsuchon P, Nakayama Y, Provencher KA, Rice KA, et al. Increased expression of angiogenic genes in the brains of mouse meg3-null embryos. Endocrinology. 2010;151:2243–52.
136. Braconi C, Kogure T, Valeri N, Huang N, Nuovo G, Costinean S, et al. microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer. Oncogene. 2011;30(47):4750–6.
137. Yan J, Guo X, Xia J, Shan T, Gu C, Liang Z, et al. MiR-148a regulates MEG3 in gastric cancer by targeting DNA methyltransferase 1. Med Oncol. 2014;31(3):879.
138. Lu KH, Li W, Liu XH, Sun M, Zhang ML, Wu WQ, et al. Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression. BMC Cancer. 2013;13:461.
139. Luke B, Lingner J. TERRA: telomeric repeat-containing RNA. EMBO J. 2009;28(17):2503–10.
140. Azzalin CM, Reichenbach P, Khoriauli L, Giulotto E, Lingner J. Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends. Science. 2007;318(5851):798–801.
141. Schoeftner S, Blasco MA. Chromatin regulation and non-coding RNAs at mammalian telomeres. Semin Cell Dev Biol. 2010;21(2):186–93.
142. Maicher A, Kastner L, Luke B. Telomeres and disease: enter TERRA. RNA Biol. 2012;9(6):843–9.
143. Azzalin CM, Lingner J. Telomeres: the silence is broken. Cell Cycle. 2008;7(9):1161–5.
144. Redon S, Reichenbach P, Lingner J. The non-coding RNA TERRA is a natural ligand and direct inhibitor of human telomerase. Nucleic Acids Res. 2010;38(17):5797–806.
145. Ng LJ, Cropley JE, Pickett HA, Reddel RR, Suter CM. Telomerase activity is associated with an increase in DNA methylation at the proximal subtelomere and a reduction in telomeric transcription. Nucleic Acids Res. 2009;37:1152–9.
146. Porro A, Feuerhahn S, Reichenbach P, Lingner J. Molecular dissection of telomeric repeat-containing RNA biogenesis unveils the presence of distinct and multiple regulatory pathways. Mol Cell Biol. 2010;30(20):4808–17.
147. Redon S, Zemp I, Lingner J. A three-state model for the regulation of telomerase by TERRA and hnRNPA1. Nucleic Acids Res. 2013;41(19):9117–28.
148. Flynn RL, Centore RC, O'Sullivan RJ, Rai R, Tse A, Songyang Z, et al. TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA. Nature. 2011;471(7339):532–6.
149. Chawla R, Azzalin CM. The telomerictranscriptome and SMG proteins at the crossroads. Cytogenet Genome Res. 2008;122:194–201.
150. Nergadze SG, Farnung BO, Wischnewski H, Khoriauli L, Vitelli V, Chawla R, et al. CpG-island promoters drive transcription of human telomeres. RNA Biol. 2009;15:2186–94.
151. Porro A, Feuerhahn S, Lingner J. TERRA-reinforced association of LSD1 with MRE11 promotes processing of uncapped telomeres. Cell Rep. 2014;6(4):765–76.
152. Farnung BO, Brun CM, Arora R, Lorenzi LE, Azzalin CM. Telomerase efficiently elongates highly transcribing telomeres in human cancer cells. PLoS One. 2012;7(4):e35714.
153. Schneider C, King RM, Philipson L. Genes specifically expressed at growth arrest of mammalian cells. Cell. 1988;54:787–93.
154. Eddy SR. Noncoding RNA, genes. Curr Opin Genet Dev. 1999;9(6):695–9.
155. Kino T, Hurt DE, Ichijo T, Nader N, Chrousos GP. Noncoding RNA gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor. Sci Signal. 2010;3(107):ra8.
156. Mourtada-Maarabouni M, Pickard MR, Hedge VL, Farzaneh F, Williams GT. GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene. 2009;28(2):195–208.
157. Nakamura Y, Takahashi N, Kakegawa E, Yoshida K, Ito Y, Kayano H, et al. The GAS5 (growth arrest-specific transcript 5) gene fuses to BCL6 as a result of t(1;3)(q25;q27) in a patient with B-cell lymphoma. Cancer Genet Cytogenet. 2008;182(2):144–9.
158. Shi X, Sun M, Liu H, Yao Y, Kong R, Chen F, et al. A critical role for the long non-coding RNA GAS5 in proliferation and apoptosis in non-small-cell lung cancer. Mol Carcinog. 2013. doi:10.1002/mc.22120.
159. Liu Z, Wang W, Jiang J, Bao E, Xu D, Zeng Y, et al. Downregulation of GAS5 promotes bladder cancer cell proliferation, partly by regulating CDK6. PLoS One. 2013;8(9):e73991.
160. Lu X, Fang Y, Wang Z, Xie J, Zhan Q, Deng X, et al. Downregulation of gas5 increases pancreatic cancer cell proliferation by regulating CDK6. Cell Tissue Res. 2013;354(3):891–6.
161. Zhang Z, Zhu Z, Watabe K, Zhang X, Bai C, Xu M, et al. Negative regulation of lncRNA GAS5 by miR-21. Cell Death Differ. 2013;20(11):1558–68.
162. 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.
163. 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.
164. Kim K, Choi J, Heo K, Kim H, Levens D, Kohno K, et al. Isolation and characterization of a novel H1.2 complex that acts as a repressor of p53-mediated transcription. J Biol Chem. 2008;283:9113–26.
165. Denisenko ON, Bomsztyk K. The product of the murine homolog of the Drosophila extra sex combs gene displays transcriptional repressor activity. Mol Cell Biol. 1997:4707–17.
166. Wang G, Li Z, Zhao Q, Zhu Y, Zhao C, Li X, et al. LincRNA-p21 enhances the sensitivity of radiotherapy for human colorectal cancer by targeting the Wnt/β-catenin signaling pathway. Oncol Rep. 2014;31(4):1839–45.
167. Hung T, Wang Y, Lin MF, Koegel AK, Kotake Y, Grant GD, et al. Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nat Genet. 2011;43(7):621–9.
168. Morachis JM, Murawsky CM, Emerson BM. Regulation of the p53 transcriptional response by structurally diverse core promoters. Genes Dev. 2010;24:135–47.
169. Young TL, Matsuda T, Cepko CL. The noncoding RNA taurine upregulated gene 1 is required for differentiation of the murine retina. Curr Biol. 2005;15:501–12.
170. Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A. 2009;106(28):11667–72.
171. Han Y, Liu Y, Gui Y, Cai Z. Long intergenic non-coding RNA TUG1 is overexpressed in urothelial carcinoma of the bladder. J Surg Oncol. 2013;107(5):555–9.
172. Zhang Q, Geng PL, Yin P, Wang XL, Jia JP, Yao J. Down-regulation of long non-coding RNA TUG1 inhibits osteosarcoma cell proliferation and promotes apoptosis. Asian Pac J Cancer Prev. 2013;14(4):2311–5.
173. Lustig O, Ariel I, Ilan J, Lev-Lehman E, De-Groot N, Hochberg A. Expression of the imprinted gene H19 in the human fetus. Mol Reprod Dev. 1994;38(3):239–46.
174. Gabory A, Jammes H, Dandolo L. The H19 locus: role of an imprinted non-coding RNA in growth and development. Bioessays. 2010;32(6):473–80.
175. Hibi K, Nakamura H, Hirai A, Fujikake Y, Kasai Y, Akiyama S, et al. Loss of H19 imprinting in esophageal cancer. Cancer Res. 1996;56(3):480–2.
176. Matouk IJ, DeGroot N, Mezan S, Ayesh S, Abu-lail R, Hochberg A, et al. The H19 non-coding RNA is essential for human tumor growth. PLoS One. 2007;2(9):e845.
177. Berteaux N, Lottin S, Monte D, Pinte S, Quatannens B, Coll J, et al. H19 mRNA-like noncoding RNA promotes breast cancer cell proliferation through positive control by E2F1. J Biol Chem. 2005;280(33):29625–36.
178. Yang F, Bi J, Xue X, Zheng L, Zhi K, Hua J, et al. Up-regulated long non-coding RNA H19 contributes to proliferation of gastric cancer cells. FEBS J. 2012;279(17):3159–65.
179. Shi Y, Wang Y, Luan W, Wang P, Tao T, Zhang J, et al. Long non-coding RNA H19 promotes glioma cell invasion by deriving miR-675. PLoS One. 2014;9(1):e86295.
180. Yoshimizu T, Miroglio A, Ripoche MA, Gabory A, Vernucci M, Riccio A, et al. The H19 locus acts in vivo as a tumor suppressor. Proc Natl Acad Sci U S A. 2008;105(34):12417–22.
181. Hao Y, Crenshaw T, Moulton T, Newcomb E, Tycko B. Tumour-suppressor activity of H19 RNA. Nature. 1993;365(6448):764–7.
182. Cai X, Cullen BR. The imprinted H19 noncoding RNA is a primary microRNA precursor. RNA. 2007;13(3):313–6.
183. Tsang WP, Ng EK, Ng SS, Jin H, Yu J, Sung JJ, et al. Oncofetal H19- derived miR-675 regulates tumor suppressor RB in human colorectal cancer. Carcinogenesis. 2010;31(3):350–8.
184. Hajjari M, Khoshnevisan A, Lemos B. Characterizing the Retinoblastoma 1 locus: putative elements for Rb1 regulation by in silico analysis. Front Genet. 2014;5:2.
185. Jinno Y, Ikeda Y, Yun K, Maw M, Masuzaki H, Fukuda H, et al. Establishment of functional imprinting of the H19 gene in human developing placentae. Nat Genet. 1995;10(3):318–24.
186. Kopf E, Bibi O, Ayesh S, Tykocinski M, Vitner K, Looijenga LH, et al. The effect of retinoic acid on the activation of the human H19 promoter by a 3' downstream region. FEBS Lett. 1998;432(3):123–7.
187. Barsyte-Lovejoy D, Lau SK, Boutros PC, Khosravi F, Jurisica I, Andrulis IL, et al. The c-Myc oncogene directly induces the H19 noncoding RNA by allele-specific binding to potentiate tumorigenesis. Cancer Res. 2006;66(10):5330–7.
188. Adriaenssens E, Lottin S, Dugimont T, Fauquette W, Coll J, Dupouy JP, et al. Steroid hormones modulate H19 gene expression in both mammary gland and uterus. Oncogene. 1999;18(31):4460–73.
189. Dugimont T, Montpellier C, Adriaenssens E, Lottin S, Dumont L, Iotsova V, et al. The H19 TATA-less promoter is efficiently repressed by wild-type tumor suppressor gene product p53. Oncogene. 1998;16(18):2395–401.
190. Farnebo M, Bykov VJ, Wiman KG. The p53 tumor suppressor: a master regulator of diverse cellular processes and therapeutic target in cancer. Biochem Biophys Res Commun. 2010;396(1):85–9.
191. Matouk IJ, Raveh E, Abu-Lail R, Mezan S, Gilon M, Gershtain E, et al. Oncofetal H19 RNA promotes tumor metastasis. Biochim Biophys Acta. 2014;1843(7):1414–26.
192. Chen B, Yu M, Chang Q, Lu Y, Thakur C, Ma D, et al. Mdig de-represses H19 large intergenic non-coding RNA (lincRNA) by down-regulating H3K9me3 and heterochromatin. Oncotarget. 2013;4(9):1427–37.
193. Berteaux N, Lottin S, Monté D, Pinte S, Quatannens B, Coll J, et al. H19 mRNA-like noncoding RNA promotes breast cancer cell proliferation through positive control by E2F1. J Biol Chem. 2005;280(33):29625–36.
194. Luo M, Li Z, Wang W, Zeng Y, Liu Z, Qiu J. Upregulated H19 contributes to bladder cancer cell proliferation by regulating ID2 expression. FEBS J. 2013;280(7):1709–16.
195. Ayesh S, Matouk I, Schneider T, Ohana P, Laster M, Al-Sharef W, et al. Possible physiological role of H19 RNA. Mol Carcinog. 2002;35(2):63–74.
196. Banet G, Bibi O, Matouk I, Ayesh S, Laster M, Kimber KM, et al. Characterization of human and mouse H19 regulatory sequences. Mol Biol Rep. 2000;27(3):157–65.
197. Sidi AA, Ohana P, Benjamin S, Shalev M, Ransom JH, Lamm D, et al. Phase I/II marker lesion study of intravesical BC-819 DNA plasmid in H19 over expressing superficial bladder cancer refractory to bacillus calmette-guerin. J Urol. 2008;180(6):2379–83.
198. Matouk I, Raveh E, Ohana P, Lail RA, Gershtain E, Gilon M, et al. The increasing complexity of the oncofetal h19 gene locus: functional dissection and therapeutic intervention. Int J Mol Sci. 2013;14(2):4298–316.
199. Yu M, Ohira M, Li Y, Niizuma H, Oo ML, Zhu Y, et al. High expression of ncRAN, a novel non-coding RNA mapped to chromosome 17q25.1, is associated with poor prognosis in neuroblastoma. Int J Oncol. 2009;34(4):931–8.
200. Zhu Y, Yu M, Li Z, Kong C, Bi J, Li J, et al. ncRAN, a newly identified long noncoding RNA, enhances human bladder tumor growth, invasion, and survival. Urology. 2011;77(2):510.e1.
201. Qi P, Xu MD, Ni SJ, Shen XH, Wei P, Huang D, et al. Down-regulation of ncRAN, a long non-coding RNA, contributes to colorectal cancer cell migration and invasion and predicts poor overall survival for colorectal cancer patients. Mol Carcinog. 2014. doi:10.1002/mc.22137.