Open Access Journal Article

How Does Lncrna Regulation Impact Cancer Metastasis

by Abreto Devit Mancheng a  and  Ugwemubwem Ossas a,*
Internal Medicine, Hopital du Mali, Bamako, Mali.
Author to whom correspondence should be addressed.
CI  2022, 6; 1(1), 6;
Received: 19 May 2022 / Accepted: 7 June 2022 / Published Online: 14 June 2022


Metastasis is the major cause of cancer-related mortality. Metastasis is a process through which cancer spreads from its initial location to other sections of the body. Cancer cells' epithelial-mesenchymal transition (EMT), anoikis resistance, cell migration, and angiogenesis are all well-known steps in this process. Investigating the molecular processes that govern cancer metastatic progression may lead to more effective diagnostic and treatment strategies. Long non-coding RNAs (lncRNAs) have recently discovered to have a vital more than 200 nucleotides. A rising body of research indicates that lncRNAs have a role in a wide range of biological processes and diseases, including cancer. The usage of LncRNA in cancer metastasis has been widely researched. However, according to current studies, lncRNA is mostly associated with the EMT process. This review focuses on the processes behind lncRNA involvement in cancer metastasis.

Copyright: © 2022 by Mancheng and Ossas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (Creative Commons Attribution 4.0 International License). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Show Figures

Share and Cite

ACS Style
Mancheng, A. D.; Ossas, U. How Does Lncrna Regulation Impact Cancer Metastasis. Cancer Insight, 2022, 1, 6.
AMA Style
Mancheng A D, Ossas U. How Does Lncrna Regulation Impact Cancer Metastasis. Cancer Insight; 2022, 1(1):6.
Chicago/Turabian Style
Mancheng, Abreto D.; Ossas, Ugwemubwem 2022. "How Does Lncrna Regulation Impact Cancer Metastasis" Cancer Insight 1, no.1:6.
APA style
Mancheng, A. D., & Ossas, U. (2022). How Does Lncrna Regulation Impact Cancer Metastasis. Cancer Insight, 1(1), 6.

Article Metrics

Article Access Statistics


  1. Gupta G, P, Massague J. Cancer metastasis: Building a framework 2006. Cell 127:679- 695. doi:10.1016/j.cell.2006.11.001
  2. Shi Z, Wei Q, She J. MicroRNAs in gastric cancer metastasis. Crit. Rev. Eukaryot. Gene Expr. 2014; 24:39 -53. doi:10.1615/CritRevEukaryotGeneExpr.2014007896
  3. Shen X, H Qi, P Du. Long non- coding RNAs in cancer invasion and metastasis. Mod. Pathol. 2015; 28(1):4 -13. doi:10.1038/modpathol.2014.75
  4. Zhang Y, Yang P, Wang X F. Microenvironmental regulation of cancer metastasis by miRNAs. Trends Cell Biol. 2014; 24:153-160 . doi:10.1016/j.tcb.2013.09.007
  5. Bouyssou J M , Manier S et al. Regulation of microRNAs in cancer metastasis. Biochim. Biophys. Acta 2014; 1845:255 -265. doi:10.1016/j.bbcan.2014.02.002
  6. Mercer, T R, Mattick, J S. Structure and function o f long noncoding RNAs in epigenetic regulation. Nat. Struct. Mol. Biol. 20:300-307; 2013. doi:10.1038/nsmb.2480
  7. Wang KC, Chang H. Molecular mechanisms of long noncoding RNAs. Mol. Cell 2011; 43:904- 914. doi:10.1016/j.molcel.2011.08.018
  8. Loewer S, Cabili MN, Guttman M, et al. Large intergenic non -coding RNARoR modulates reprogramming of human induced pluripotent stem cells. Nat. Genet. 2010; 42:1113- 1117. doi:10.1038/ng.710
  9. Gupta, RA, Shah N, Wang KC, et al. Long non- coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 2010; 464:1071 -1076 .doi:10.1038/nature08975
  10. Venkatraman A, He XC, Thorvaldsen JL, et al. Maternal imprinting at the H19 -Igf2 locus maintains adult haematopoietic stem cell quiescence. Nature 2013; 500:345 -349. doi:10.1038/nature12303
  11. Yoon JH, Abdelmohsen K, Kim J, et al. Function of long non -coding RNA HOTAIR in protein ubiquitination. Nat. Commun. 2013; 4:2939 .doi:10.1038/ncomms3939
  12. Xue Y, Gu D, Ma G, et al. Genetic variants in lncRNA HOTAIR are associated with risk of colorectal cancer. 2015Mutagenesis 30(2):303 -310; doi:10.1093/mutage/geu076
  13. Kim K, Jutooru I, Chadalapaka G, et al. HOTAIR is a negative prognostic factor and exhibits pro -oncogenic activity in pancreatic cancer. Onco gene 2013; 32:1616-1625; doi:10.1038/onc.2012.193
  14. Geng YJ, Xie SL, et al. Large intervening non -coding RNA HOTAIR is associated with hepatocellular carcinoma progression. J. Int. Med. Res 2011; 39:2119 -2128 .doi:10.1177/147323001103900608
  15. Niinuma T, Suzuki H, Nojima M, et al. Upregulation of miR -196a and HOTAIR drive malignant character in gastrointestinal stromal tumors. Cancer Res. 2012; 72: 1126 -1136;. doi:10.1158/0008-5472.CAN-11-1803
  16. Hibi K, Nakamura H, Hirai A, et al. Loss of H19 imprinti ng in esophageal cancer. Cancer Res. 56:480 -482; 1996.
  17. Kondo M, Takahashi T. Altered genomic imprinting in the IGF2 and H19 genes in human lung cancer. Nihon Rinsho. 1996; 54:492 -496.
  18. Lottin S, Adriaenssens E, Dupressoir, et al. Overexpression of an ectopic H19 gene enhances the tumorigenic properties of breast cancer cells. Carcinogenesis 2002; 23: 1885 -1895.doi:10.1093/carcin/23.11.1885
  19. Kanduri C, Kanduri M, Liu L, et al. The kinetics of deregulation of expression by de novo methylation of the h19 imprinting control region in cancer cells. Cancer Res. 2002; 62:4545- 4548.
  20. Byun HM, Wong HL, Birnstein E , et al. IGF2 and H19 loss of imprinting in bladder cancer. Cancer Res. 2007; 67:10753 - 10758. doi:10.1158/0008-5472.CAN-07-0329
  21. Matouk IJ, Raveh E, Abu -lail R. et al. An Oncofetal H19 RNA promotes tumor metastasis. Biochim. Biophys. Acta 2014;1843:1414- 1426. doi:10.1016/j.bbamcr.2014.03.023
  22. Sun M. Xia R, Jin, F, et al. Downregulated long noncoding RNA MEG3 is associated with poor prognosis and promotes cell proliferation in gastric cancer. Tumour Biol. 35:1065 -1073; 2014. doi:10.1007/s13277-013-1142-z
  23. McMurray EN, Schmidt JV. Identification of imprinting regulators at the Meg3 differentially methylated region. Genomics 2012; 100:184- 194. doi:10.1016/j.ygeno.2012.06.001
  24. Anwar SL, Krech T, Hasemeier, et al . Loss of imprinting and allelic switching at the DLK1- MEG3 locus in human hepatocellular carcinoma. PLoS One 2012; 7:e49462. doi:10.1371/journal.pone.0049462
  25. Benetatos L, Hatzimichael E, Dasoula A, et al. Methylation analysis of the MEG3 and SNRPN imprinted genes in acute myeloid leukemia and my elodysplastic syndromes. Leuk. Res. 2010; 34:148 -153. doi:10.1016/j.leukres.2009.06.019
  26. Augoff K,McCue B, Plow EF, et al. MiR -31 and its host gene lncRNA LOC554202 are regulated by promoter hypermethylation in triple -negative breast cancer. Mol. Cancer 2012;11:5.doi:10.1186/1476-4598-11-5
  27. Shi Y, Lu J, Zhou J, et al. Long non- coding RNA Loc554202 regulates proliferation and migration in breast cancer cells. Biochem. Biophys. Res. Commun. 2014; 446:448- 453.doi:10.1016/j.bbrc.2014.02.144
  28. Pandey GK, Mitra S, Subhash S, et al. The risk -associated long noncoding RNA NBAT -1 controls neuroblastoma progression by regulating cell proliferation and neuronal differentiation. Cancer Cell 2014; 26:722- 737. doi:10.1016/j.ccell.2014.09.014
  29. Ji P,Diederichs S, Wang W, Boing S, et al. MALAT -1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early- stage nonsmall cell lung cancer. Oncogene 2003; 22:8031- 8041. doi:10.1038/sj.onc.1206928
  30. Ma KX, Wang HJ, et al. Long noncoding RNA MALAT1 associates with the malignant status and poor prognosis in glioma. Tumour Biol. 36(5):3355 doi:10.1007/s13277-014-2969-7
  31. Zheng HT, Shi DB, Wang YW, et al. High expression of lncRNA MALAT1 suggests a biomarke r of poor prognosis in colorectal cancer. Int. J. Clin. Exp. Pathol. 7:3174-3181.
  32. Liu JH, Chen G, Dang YW, et al. Expression and prognostic significance of lncRNA MALAT1 in pancreatic cancer tissues. Asian Pac. J. Cancer Prev. 2014;15:2971- 2977. doi:10.7314/APJCP.2014.15.7.2971
  33. Ren S,Liu Y,Xu W, et al. Long noncoding RNA MALAT -1 is a new potential therapeutic target for castration resistant prostate cancer. J. Urol. 2013; 190:2278- 2287. doi:10.1016/j.juro.2013.07.001
  34. Ying L, Chen Q, Wang Y, et al. MALAT -1 contributes to bladder cancer cell migration by inducing epithelial -to -mesenchymal transition. Mol. Biosyst. 2012; 8:2289- 2294. doi:10.1039/c2mb25070e
  35. Xu C, Yang M, Tian J, et al. A long non -coding RNA and its important 3¢ end functional motif in colorectal cancer metastasis. Int. J. Oncol. 2011; 39:169 -175.
  36. Jiang Y, Li Y, Fang S, et al. Role of MALAT1 correlates with HPV in cervical cancer. Oncol. Lett. 2014; 7:2135- 2141. doi:10.3892/ol.2014.1996
  37. Fan Y, Shen B, Tan M, et al. TGF -beta -induced upregulation of malat1 promotes bladder cancer metastasis by associating with suz12. Clin. Cancer Res. 2014; 20:1531- 1541. doi:10.1158/1078-0432.CCR-13-1455
  38. Shen L, Chen L, Wang Y, et al. Long noncoding RNA MALAT1 promotes brain metast asis by inducing epithelial-mesenchymal transition in lung cancer. J. Neurooncol. 2015; 121(1):101- 108. doi:10.1007/s11060-014-1613-0
  39. Miyagawa R, Tano K,Mizuno R, et al. Identification of cis - and transacting factors involved in the localization of MAL AT-1 noncoding RNA to nuclear speckles. RNA 2012; 18:738 -751. doi:10.1261/rna.028639.111
  40. Tripathi V, Ellis JD, Shen Z, et al. The nuclear -retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol . Cell 2010; 39:925-938. doi:10.1016/j.molcel.2010.08.011
  41. Wan Y, Chang HY. HOTAIR: Flight of noncoding RNAs in cancer metastasis. Cell Cycle 2010; 9:3391 -3392. doi:10.4161/cc.9.17.13122
  42. Yang Z, Zhou L, Wu LM, et al. Overexpression of long non -codin g RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann. Surg. Oncol. 2011; 18:1243- 1250. doi:10.1245/s10434-011-1581-y
  43. Liu XH, Liu ZL, et al. The long non -coding RNA HOTAIR indicates a poor prog nosis and promotes metastasis in non-small cell lung cancer. BMC Cancer 2013; 13:464. doi:10.1186/1471-2407-13-464
  44. Lv XB, Lian GY, Wang HR, et al. Long noncoding RNA HOTAIR is a prognostic marker for esophageal squamous cell carcinoma progression and s urvival. PLoS One 2013; 8:e63516. doi:10.1371/journal.pone.0063516
  45. He X, Bao W, Li X, et al. The long non- coding RNA HOTAIR is upregulated in endometrial carcinoma and correlates with poor prognosis. Int. J. Mol. Med. 2014; 33:325 -332 doi:10.3892/ijmm.2013.1570
  46. Huang L, Liao LM, Liu AW, et al. Overexpression of long noncoding RNA HOTAIR predicts a poor prognosis in patients with cervical cancer. Arch. Gynecol. Obstet. 2014; 290:717 - 723. doi:10.1007/s00404-014-3236-2
  47. Xu ZY,Yu QM, et al. Knockdow n of long non -coding RNA HOTAIR suppresses tumor invasion and reverses epithelial -mesenchymal transition in gastric cancer. Int. J. Biol. 2013; Sci. 9:587 -597. doi:10.7150/ijbs.6339
  48. Wu L,Murat P, Matak-Vinkovic D. Between long noncoding RNA HOTAIR and PRC2 proteins. Biochmistry 52:9519- 9527; 2013. doi:10.1021/bi401085h
  49. Li L, Liu B, Wapinski OL, et al. Targeted disruption of Hotair leads to homeotic transformation and gene derepression. Cell Rep. 5:3- 12; 2013. doi:10.1016/j.celrep.2013.09.003
  50. Brunkow ME, Tilghman SM. Ectopic expression of the H19 gene in mice causes prenatal lethality. Genes Dev. 5:1092 -1101; 1991. doi:10.1101/gad.5.6.1092
  51. Bartolomei MS, Zemel S, Tilghman SM. Parental imprinting of the mou se H19 gene. Nature 351:153-155; 1991. doi:10.1038/351153a0
  52. Verhaegh GW, Verkleij L, et al. Polymorphisms in the H19 gene and the risk of bladder cancer. Eur. Urol. 54:1118-1126; 2008. doi:10.1016/j.eururo.2008.01.060
  53. Medrzycki M, Zhang Y, Zhang W, et al. Histone h1.3 suppresses h19 noncoding RNA expression and cell growth of ovarian cancer cells. Cancer Res. 74:6463- 6473; 2014. doi:10.1158/0008-5472.CAN-13-2922
  54. Zhang EB, Han L, Yin DD, et al. C- Myc -induced, long, noncoding H19 affects cell prol iferation and predicts a poor prognosis in patients with gastric cancer. Med. Oncol. 31:914; 2014. doi:10.1007/s12032-014-0914-7
  55. Murphy SK, Huang Z, Wen Y, et al. Frequent IGF2/H19 domain epigenetic alterations and elevated IGF2 expression in epithelia l ovarian cancer. Mol. Cancer Res. 4:283- 292; 2006. doi:10.1158/1541-7786.MCR-05-0138
  56. Berteaux N, Lottin S, Monte D, et al. H19 mRNA -like noncoding RNA promotes breast cancer cell proliferation through positive control by E2F1. J. Biol. Chem. 280:29625- 29636; 2005. doi:10.1074/jbc.M504033200
  57. Chen CL, Ip SM, Cheng D, et al. Imprinting of the IGF -II and H19 genes in epithelial ovarian cancer. Clin. Cancer Res. 6:474 -479; 2000.
  58. Kondo M, Suzuki H, et al. Frequent loss of imprinting of the H19 gene is often associated with its overexpression in human lung cancers. Oncogene 10:1193 -1198; 1995.
  59. Ma C, Nong K, Zhu H, et al. H19 promotes pancreatic cancer metastasis by derepressing let- 7's suppression on its target HMGA2- mediated EMT. Tumour Bio l. 35:9163-9169; 2014. doi:10.1007/s13277-014-2185-5
  60. Tsang WP, Ng EK, et al. H19 -derived miR -675 regulates tumor suppressor RB in human colorectal cancer. Carcinogenesis 2010; 31:350 -358 . doi:10.1093/carcin/bgp181
  61. Shi Y, Wang Y, Luan W, et al. Long non -coding RNA H19 promotes glioma cell invasion by deriving miR -675. 2014; PLoS One 9:e86295. doi:10.1371/journal.pone.0086295
  62. Zhu M,Chen Q, Liu X, et al. lncRNA H19/ miR -675 axis represses prostate cancer metastasis by targeting TGFBI. FEBS J. 2014; 281:3766 -3775. doi:10.1111/febs.12902
  63. Lv J, Ma L, Chen XL, et al. Downregulation of LncRNAH19 and MiR -675 promotes migration and invasion of human hepatocellular carcinoma cells through AKT/GSK -3beta/Cdc25A signaling pathway. J. Huazhong Univ. Sci. Te chnolog. Med. Sci. 2014; 34:363- 369. doi:10.1007/s11596-014-1284-2
  64. Ariel I, Lustig O, Schneider T, et al. The imprinted H19 gene as a tumor marker in bladder carcinoma. Urology 1995; 45:335 -338. doi:10.1016/0090-4295(95)80030-1
  65. Atala A, Re. Long no n-coding RNA H19 increases bladder cancer metastasis by associating with EZH2 and inhibiting E -cadherin expression. J. Urol. 2013; 190:2306. doi:10.1016/j.juro.2013.08.057
  66. Luo M, Li Z, Wang W, et al. Long non -coding RNA H19 increases bladder cancer met astasis by associating with EZH2 and inhibiting E-cadherin expression. Cancer Lett. 2013;333:213- 221. doi:10.1016/j.canlet.2013.01.033
  67. Zhang L, Yang F, Yuan JH et al. Epigenetic activation of the MiR -200 family contributes to H19 -mediated metastasis su ppression in hepatocellular carcinoma. Carcinogenesis 34:577- 586; 2013. doi:10.1093/carcin/bgs381
  68. Bi HS, Yang XY, Yuan JH, et al. H19 inhibits RNA polymerase II -mediated transcription by disrupting the hnRNP U -actin complex. Biochim. Biophys. Acta 1830 :4899-4906 2013 . doi:10.1016/j.bbagen.2013.06.026
  69. Coccia EM, Cicala C, Charlesworth, et al. Regulation and expression of a growth arrest- specific gene (gas5) during growth, differentiation, and development. Mol. Cell Biol. 1992; 12:3514 -3521. doi:10.1128/MCB.12.8.3514
  70. Nakamura Y, Takahashi N, Kakegawa E, 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. 182:144- 149; 2008. doi:10.1016/j.cancergencyto.2008.01.013
  71. Cao S, Liu W, Li F, et al. Decreased expression of lncRNA GAS5 predicts a poor prognosis in cervical cancer. Int. J. Clin. Exp. Pathol. 2014; 7:6776 -6783.
  72. Sun M, Jin FY, Xia R, et al. Decreased exp ression of long noncoding RNA GAS5 indicates a poor prognosis and promotes cell proliferation in gastric cancer. BMC Cancer 2014; 14:319. doi:10.1186/1471-2407-14-319
  73. Tu ZQ, Li RJ, et al. Down -regulation of long non -coding RNA GAS5 is associated with t he prognosis of hepatocellular carcinoma. Int. J. Clin. Exp. Pathol. 2014; 7:4303 -4309.
  74. Yin D, He X, Zhang E, et al. Long noncoding RNA GAS5 affects cell proliferation and predicts a poor prognosis in patients with colorectal cancer. Med. Oncol. 2014; 31:253. doi:10.1007/s12032-014-0253-8
  75. Krell J, Frampton AE, Mirnezami R, et al. Growth arrest -specific transcript 5 associated snoRNA levels are related to p53 expression and DNA.
  76. Rosa AL, Wu YQ, Kwabi-Addo, et al. specific methylation of a functional CTCF binding site upstream of MEG3 in the human imprinted domain of 14q32. Chromosome Res. 2005; 13:809 -818. doi:10.1007/s10577-005-1015-4
  77. Zhang X, Zhou Y, Mehta KR, et al. A pituitary -derived MEG3 isoform functions as a growth suppressor in tumor cells. J. Clin. Endocrinol. Metab. 2003; 88:5119 -5126. doi:10.1210/jc.2003-030222
  78. Zhao J, Dahle D, Zhou Y, et al. Hypermethylation of the promoter region is associated with the loss of MEG3 gene expression in human pituitary tumors. J. Clin. End ocrinol. Metab. 2005; 90:2179-2186. doi:10.1210/jc.2004-1848
  79. Benetatos L, Vartholomatos G, Hatzimichael E. MEG3 imprinted gene contribution in tumorigenesis. Int. J. Cancer 2011: 129:773 -779. doi:10.1002/ijc.26052
  80. Braconi C, Kogure T, Valeri N, et al. microRNA -29 can regulate expression of the long non -coding RNA gene MEG3 in hepatocellular cancer. Onco gene 2011; 30:4750-4756. doi:10.1038/onc.2011.193
  81. Yan J, Guo X, Xia J, et al. Regulates MEG3 in gastric cancer by targeting DNA methyltransferase 1. Med. Oncol. 2014; 31:879. doi:10.1007/s12032-014-0879-6
  82. Li Z, Li C, Liu C, et al. Expression of the long non -coding RNAs MEG3, HOTAIR, and MALAT -1 in non -functioning pituitary adenomas and their relationship to tumor behavior. Pituitary 2015; 18(1):42- 47. doi:10.1007/s11102-014-0554-0
  83. Jia LF, Wei SB, Gan YH, et al. Expression, regulation and roles of miR -26a and MEG3 in tongue squamous cell carcinoma. Int. J. Cancer 135:2282 -2014; 2293. doi:10.1002/ijc.28667
  84. Lu KH, Li W, Liu X, et al. Long non -coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression. BM C Cancer 2013; 13:461. doi:10.1186/1471-2407-13-461
  85. Yin DD, Liu ZJ, Zhang E, et al. Decreased expression of long noncoding RNA MEG3 affects cell proliferation and predicts a poor prognosis in patients with colorectal cancer. Tumour Biol. 2015; 36(6):4 851-4859. doi:10.1007/s13277-015-3139-2
  86. Zhou Y, Zhong Y,Wang Y, et al. Activation of p53 by MEG3 non -coding RNA. J. Biol. Chem. 2007; 282:24731 -24742.
  87. Panzitt K, Tschernatsch M. et al. Characterization of HULC, a novel gene with striking up -regulation in hepatocellular carcinoma, as noncoding RNA. Gastroenterology 132:330- 342; 2007. doi:10.1053/j.gastro.2006.08.026
  88. Matouk IJ, Abbasi I, Hochberg A, et al. Highly upregulated in liver cancer noncoding RNA is overexpressed in hepatic colorectal metastasis. Eur. J. Gastroenterol. Hepatol. 2009; 21:688- 692. doi:10.1097/MEG.0b013e328306a3a2
  89. Hammerle M,Gutschner T, Uckelmann H, et al. Posttranscriptional destabilization of the liver -specific long noncoding RNA HULC by the IGF2 mRNA -binding protein 1 (IGF2BP1). Hepatology2013; 58:1703 -1712. doi:10.1002/hep.26537
  90. Wang J, Liu X, Wu H, et al. CREB up -regulates long non -coding RNA, HULC expression through interaction with microRNA -372 in liver cancer. Nucleic Acids Res. 2010; 38:5366-5383. doi:10.1093/nar/gkq285
  91. Zhao Y, Guo Q, et al. 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; 31:358- 364. doi:10.3892/or.2013.2850
  92. Wang Y, Solt LA, et al. Regulation of p53 stability and apoptosis by a ROR agonist. PLoS One 2012; 7:e34921. doi:10.1371/journal.pone.0034921
  93. Zhang A, Zhou N, Huang J, Liu Q, et al. Human long non- coding RNA-RoR is a p53 repressor in respons e to DNA damage. Cell Res. 2013; 23:340-350. doi:10.1038/cr.2012.164
  94. Wang Y, Xu Z, Jiang J, et al. Endogenous miRNA sponge lincRNA -RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self -renewal. Dev. Cell. 2013; 25:69- 80. doi:10.1016/j.devcel.2013.03.002
  95. Hou P, Zhao Y, Li Z, et al. LincRNA -ROR induces epithelial- to-mesenchymal transition and contributes to breast cancer tumorigenesis and metastasis. Cell Death Dis. 2014; 5:e1287. doi:10.1038/cddis.2014.249
  96. Eades G, Wolfson B, et al. lincRNA -RoR and miR -145 regulate invasion in triplenegative breast cancer via targeting ARF6. Mol. Cancer Res. 2015; 13(2):330- 338. doi:10.1158/1541-7786.MCR-14-0251
  97. Yuan JH, Yang F, Wang F, et al. A long noncoding RNA activated by TGFbeta promotes the invasion -metastasis cascade in hepatocellular carcinoma. Cancer Cell 2014; 25:666- 681. doi:10.1016/j.ccr.2014.03.010
  98. Li W, Kang Y. A new Lnc in metastasis: Long noncoding RNA mediates the prometastatic functions of TGFbeta. Cancer Cell 2014; 25:557- 559. doi:10.1016/j.ccr.2014.04.014
  99. Poliseno L, Salmena L, Zhang J, et al. A coding -independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 2010; 465:1033- 1038. doi:10.1038/nature09144
  100. Yu G, Yao W, Gumireddy K, et al. Pseudogene PTENP1 functions as a competing endogenous RNA to suppress clear cell renal cell carcinoma progression. Mol. Cancer Ther. 2014; 13(12):3086- 3097. doi:10.1158/1535-7163.MCT-14-0245
  101. Poliseno L, Haimovic A, et al. Deletion of PTENP1 pseudogene in human melanoma. J. Invest. Dermatol. 2011; 131:2497- 2500. doi:10.1038/jid.2011.232
  102. Yu G, Yao W, Gumireddy K, et al. Pseudogene PTENP1 functions as a competing endogenous RNA to suppress clear -cell renal cell carcinoma progression. Mol. Cancer Ther. 2014; 13:3086 -3097. doi:10.1158/1535-7163.MCT-14-0245
  103. Meng J, Li P, Zhang Q, et al. A four- long non -coding RNA signature in predicting breast cancer survival. J. Exp. Clin. Cancer Res. 2014;33:84. doi:10.1186/s13046-014-0084-7
  104. Grote P, Wittler L, Hendrix D, et al. The tissue -specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse. Dev. Cell 2013; 24:206- 214. doi:10.1016/j.devcel.2012.12.012
  105. Xu TP, Huang MD, et al. Decreased expr ession of the long noncoding RNA FENDRR is associated with poor prognosis in gastric cancer and FENDRR regulates gastric cancer cell metastasis by affecting fibronectin1 expression. J. Hematol. Oncol. 2014; 7:63. doi:10.1186/s13045-014-0063-7
  106. LaFlamme B, GAPLINC and gastric cancer. Nat. Genet. 2014; 46:1159. doi:10.1038/ng.3136
  107. Hu Y, Wang J, Qian J, et al. Long noncoding RNA GAPLINC regulates CD44 -dependent cell invasiveness and associates with poor prognosis of gastric cancer. Cancer Res. 2014; 7 4(23):6890-6902. doi:10.1158/0008-5472.CAN-14-0686
  108. Sun NX, Ye C, Zhao Q, et al. Long noncoding RNA -EBIC promotes tumor cell invasion by binding to EZH2 and repressing E -cadherin in cervical cancer. PLoS One 2014; 9:e100340. doi:10.1371/journal.pone.0100340
  109. Johnson SM, Grosshans H, et al. Labourier, E.; Reinert, K. L.; Brown, D.; Slack, F. J. RAS is regulated by the let -7 microRNA family. Cell 2005; 120:635 -647. doi:10.1016/j.cell.2005.01.014
  110. Gao Y, Wu F, Zhou J, et al. The H19/let -7 double -ne gative feedback loop contributes to glucose metabolism in muscle cells. Nucleic Acids Res. 2014; 42(22):13799 -13811. doi:10.1093/nar/gku1160
  111. Kallen AN, Zhou XB, Xu J, et al. The imprinted H19 lncRNA antagonizes let- 7 microRNAs. Mol. Cell 2013; 52:101-
  112. doi:10.1016/j.molcel.2013.08.027112.ShenL,WanZ,MaY,etal.TheclinicalutilityofmicroRNA-21asnovelbiomarkerfordiagnosinghumancancers.TumourBiol.2015;36(3):1993-2005.doi:10.1007/s13277-014-2806-z
  113. Zhang Z, Zhu Z, Watabe K, et al. Negative regulation of lncRNA GAS5 by miR -21. Cell Death Differ. 2013; 20:1558- 1568. doi:10.1038/cdd.2013.110
  114. Leucci E, Patella F, Waage J, et al. MicroRNA -9 targets the long non -coding RNA MALAT1 for degradation in the nucleus. Sci. Rep. 2013; 3:2535. doi:10.1038/srep02535
  115. Smits G, Mungall AJ, Griffiths-Jones S, et al. Conservation of the H19 noncoding RNA and H19 -IGF2 imprinting mechanism in therians. Nat. Genet. 2008; 40:971- 976. doi:10.1038/ng.168
  116. Keniry A, Oxley D, Monnier P, et al. The H19 lincRNA is a developmental reservoir of miR -675 that suppresses growth and Igf1r. Nat. Cell Biol. 2012; 14:659- 665. doi:10.1038/ncb2521
  117. Li H, Yu B, Li J, et al. Overexpression of lncRNA H19 enhances carcinogen esis and metastasis of gastric cancer. Oncotarget 2014; 5:2318-2329. doi:10.18632/oncotarget.1913
  118. Zhuang M, Gao W, et al. The long non- coding RNA H19 -derived miR -675 modulates human gastric cancer cell proliferation by targeting tumor suppressor RUNX1. Biochem. Biophys. Res. Commun. 2014; 448:315 - 322. doi:10.1016/j.bbrc.2013.12.126
  119. Xi S, Yang M, Tao Y, et al. Cigarette smoke induces C/EBP -beta -mediated activation of miR -31 in normal human respiratory epithelia and lung cancer cells. PLoS One 2010; 5:e13764. doi:10.1371/journal.pone.0013764
  120. Wang J, Tsouko E, Jonsson P, et al. miR -206 inhibits cell migration through direct targeting of the actin -binding protein Coronin 1C in triple -negative breast cancer. Mol. Oncol. 2014; 8:1690 -1702. doi:10.1016/j.molonc.2014.07.006
  121. Duan FT, Qian F, Fang K, et al. miR -133b, a muscle- specific microRNA, is a novel prognostic marker that participates in the progression of human colorectal cancer via regulation of CXCR4 expression. Mol. Cancer 2013;12:164. doi:10.1186/1476-4598-12-164
  122. Liz J, Portela A, Soler M, et al. Regulation of pri -miRNA processing by a long noncoding RNA transcribed from an ultraconserved region. Mol. Cell 2014; 55:138- 147. doi:10.1016/j.molcel.2014.05.005
  123. Cesana M, Cacchiarelli D, Legnini I, et al. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 2011; 147:358- 369. doi:10.1016/j.cell.2011.09.028
  124. Tinzl M, Marberger M, Horvath S, et al. DD3PCA3 RNA analysis in urine --A new perspective for detecting prostate cancer. Eur. Urol. 2004; 46:182- 186. doi:10.1016/j.eururo.2004.06.004
  125. Hessels D, Klein Gunnewiek JM, et al. DD3(PCA3) -based molecular urine analysis for the diagnosis of prostate cancer. Eur. Urol. 2 003; 44:8-15; discussion 15 -16. doi:10.1016/S0302-2838(03)00201-X
  126. Jung M, Xu C, Spethmann J, et al. DD3(PCA3) -based molecular urine analysis for the diagnosis of prostate cancer. Eur. Urol. 2003; 44:8 -16. doi:10.1016/S0302-2838(03)00201-X
  127. Costa F F, Non-coding RNAs and new opportunities for the private sector. Drug Discov. Today 2009; 14:446-452. doi:10.1016/j.drudis.2009.01.008
  128. Hung T, Chang HY. Long noncoding RNA in genome regulation: Prospects and mechanisms. RNA Biol. 2010; 7:582 - 585. doi :10.4161/rna.7.5.13216
  129. Tsai MC, Spitale RC, Chang HY. Long intergenic noncoding RNAs: New links in cancer progression. Cancer Res. 2011; 71:3 -7. doi:10.1158/0008-5472.CAN-10-2483
  130. Morris KV. RNA -directed transcriptional gene silencing and activati on in human cells. Oligonucleotides 2009; 19:299- 306. doi:10.1089/oli.2009.0212
  131. Luo M, Li Z, Wang W, et al. Upregulated H19 contributes to bladder cancer cell proliferation by regulating ID2 expression. FEBS J. 2013; 280:1709 -1716. doi:10.1111/febs.12185
  132. Smaldone MC, Davies BJ. BC -819, A plasmid comprising the H19 gene regulatory sequences and diphtheria toxin A, for the potential targeted therapy of cancers. Curr. Opin. Mol. Ther. 2010; 12:607- 616.
  133. Gofrit ON, Benjamin S, Halachmi S, et al. DNA b ased therapy with diphtheria toxin -A BC- 819: a phase 2b marker lesion trial in patients with intermediate risk nonmuscle invasive bladder cancer. J. Urol. 2014;191:1697- 1702. doi:10.1016/j.juro.2013.12.011
  134. Amit D, Hochberg A. Development of targeted therapy for bladder cancer mediated by a double promoter plasmid expressing diphtheria toxin under the control of H19 and IGF2- P4 regulatory sequences. J. Transl. Med. 2010; 8:134. doi:10.1186/1479-5876-8-134
  135. Amit D, Tamir S, Birman T, et al. A Development of targeted therapy for bladder cancer mediated by a double promoter plasmid expressing diphtheria toxin under the control of IGF2- P3 and IGF2-P4 regulatory sequences. Int. J. Clin. Exp. Med. 2011; 4:91 -102. doi:10.1186/1479-5876-8-134
  136. Scaiewicz V, Sorin V, Fellig Y, et al. Use of H19 gene regulatory sequences in DNA -based therapy for pancreatic cancer. J. Oncol. 2010:178174. doi:10.1155/2010/178174
  137. Mizrahi A, Czerniak A, Levy T, et al. Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences. J. Transl. Med. 2009; 7:69. doi : 10.1186/1479 -5876 -7 -69
  138. Amit D, Hochberg A. Development of targeted therapy for a broad spectrum of cancers (pancreatic c ancer, ovarian cancer, glioblastoma and HCC) mediated by a double promoter plasmid expressing diphtheria toxin under the control of H19 and IGF2-P4 regulatory sequences. Int. J. Clin. Exp. Med. 2012; 5:296 -305.