The role of the oncofetal H19 lncRNA in tumor metastasis: Orchestrating the EMT-MET decision

Oncotarget

Volumn 7, Issue 4, 2016, Pages 3748-3765

  Matouk, Imad J ^a,b   Halle, David ^a   Raveh, Eli ^a   Gilon, Michal ^a   Sorin, Vladimir ^a   Hochberg, Avraham ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^b AL QUDS UNIVERSITY   (Palestine)

Author keywords

EMT; H19; lncRNA; MET; Metastasis; miR 675

Indexed keywords

BETA CATENIN; HIGH MOBILITY GROUP A2 PROTEIN; MICRORNA; MICRORNA 200; MICRORNA 675; MICRORNA LET 7; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; SCATTER FACTOR; SMALL UNTRANSLATED RNA; TRANSCRIPTION FACTOR EZH2; TRANSCRIPTION FACTOR SLUG; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; UVOMORULIN; WNT PROTEIN; H19 LONG NON-CODING RNA; LONG UNTRANSLATED RNA;

ARTICLE; BRAIN METASTASIS; CELL TRANSFORMATION; EPIGENETICS; EPITHELIAL MESENCHYMAL TRANSITION; GENE; GENE EXPRESSION; GENE FUNCTION; H19 GENE; HUMAN; HYPOXIA; LIVER METASTASIS; LUNG METASTASIS; MESENCHYMAL TO EPITHELIAL TRANSITION; METASTASIS; MOLECULAR PATHOLOGY; MULTIDRUG RESISTANCE; NONHUMAN; PHENOTYPE; TRANSLATIONAL RESEARCH; GENE EXPRESSION REGULATION; GENETICS; NEOPLASM; PATHOLOGY;

EPITHELIAL-MESENCHYMAL TRANSITION; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MICRORNAS; NEOPLASM METASTASIS; NEOPLASMS; RNA, LONG NONCODING;

EID: 84957991109     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.6387     Document Type: Article

References (111)

1. Rhim AD, Mirek ET, Aiello NM, Maitra A, Bailey JM, McAllister F, Reichert M, Beatty GL, Rustgi AK, Vonderheide RH, Leach SD, Stanger BZ. EMT and dissemination precede pancreatic tumor formation. Cell. 2012;148:349-361.
2. Joyce JA, Pollard JW. Microenvironmental regulation of metastasis. Nat Rev Cancer. 2009; 9: 239-252.
3. Thiery J P. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002; 2: 442-454.
4. Labelle M, Begum S, Hynes RO. Direct signaling between platelets and cancer cells induces an epithelialmesenchymal-like transition and promotes metastasis. Cancer Cell. 2011; 20: 576-590.
5. McAllister SS, Weinberg RA. The tumour-induced systemic environment as a critical regulator of cancer progression and metastasis. Nat Cell Biol. 2014; 16:717-727.
6. Hiratsuka S, Watanabe A, Aburatani H, Maru Y. Tumourmediated up-regulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat Cell Biol. 2006; 8: 1369-1375.
7. Kaplan R N, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, MacDonald DD, Jin DK, Shido K, Kerns SA, Zhu Z, Hicklin D, Wu Y, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the premetastatic niche. Nature. 2005; 438: 820-827.
8. Peinado H, Aleckovic M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G, Hergueta-Redondo M, Williams C, García-Santos G, Ghajar C, Nitadori-Hoshino A, Hoffman C, Badal K, et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med. 2012; 18: 883-891.
9. Hirata H, Hinoda Y, Shahryari V, Deng G, Nakajima K, Tabatabai ZL, Ishii N, Dahiya R. Long Noncoding RNA MALAT1 Promotes Aggressive Renal Cell Carcinoma through Ezh2 and Interacts with miR-205. Cancer Res. 2015;75: 1322-1331.
10. Liu XH, Sun M, Nie FQ, Ge YB, Zhang EB, Yin DD, Kong R, Xia R, Lu KH, Li JH, De W, Wang KM, Wang ZX. Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer. 2014;13:92.
11. Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, Wang Y, Brzoska P, Kong B, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464:1071-1076.
12. Wu Y, Liu H, Shi X, Yao Y, Yang W, Song Y. The long non-coding RNA HNF1A-AS1 regulates proliferation and metastasis in lung adenocarcinoma. Oncotarget. 2015; 6:9160-9172. doi:10.18632/oncotarget.3247.
13. Cai X, Cullen BR. The imprinted H19 noncoding RNA is a primary microRNA precursor. RNA. 2007;13:313-316.
14. Ma C, Nong K, Zhu H, Wang W, Huang X, Yuan Z, Ai K. H19 promotes pancreatic cancer metastasis by derepressing let-7's suppression on its target HMGA2-mediated EMT. Tumour Biol. 2014; 35: 9163-9169.
15. Luo M, Li Z, Wang W, Zeng Y, Liu Z, Qiu J. Long noncoding RNA H19 increases bladder cancer metastasis by associating with EZH2 and inhibiting Ecadherin expression. Cancer Lett 2013, 333: 213-22.
16. Matouk IJ, Abbasi I, Hochberg A, Galun E, Dweik H, Akkawi M. Highly up-regulated in liver cancer noncoding RNA is overexpressed in hepatic colorectal metastasis. Eur J Gastroenterol Hepatol. 2009;21:688-692.
17. Yuan JH, Yang F, Wang F, Ma JZ, Guo YJ, Tao QF, Liu F, Pan W, Wang TT, Zhou CC, Wang SB, Wang YZ, Yang Y, et al. A long noncoding RNA activated by TGF-β promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell. 2014;25: 666-681.
18. Sun M, Liu XH, Wang KM, Nie FQ, Kong R, Yang JS, Xia R, Xu TP, Jin FY, Liu ZJ, Chen JF, Zhang EB, De W, Wang ZX. Down-regulation of BRAF activated non-coding RNA is associated with poor prognosis for non-small cell lung cancer and promotes metastasis by affecting epithelialmesenchymal transition. Mol Cancer. 2014; 13:68.
19. Sun M, Liu XH, Lu KH, Nie FQ, Xia R, Kong R, Yang JS, Xu TP, Liu YW, Zou YF, Lu BB, Yin R, Zhang EB, et al. EZH2-mediated epigenetic suppression of long noncoding RNA SPRY4-IT1 promotes NSCLC cell proliferation and metastasis by affecting the epithelial-mesenchymal transition. Cell Death Dis. 2014;5:e1298.
20. Qiu JJ, Lin YY, Ding JX, Feng WW, Jin HY, Hua KQ. Long non-coding RNA ANRIL predicts poor prognosis and promotes invasion/metastasis in serous ovarian cancer. Int J Oncol. 2015; 46:2497-2505.
21. Zhang EB, Kong R, Yin DD, You LH, Sun M, Han L, Xu TP, Xia R, Yang JS, De W, Chen JF. 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;5:2276-2292. doi: 10.18632/oncotarget.1902.
22. Wang F, Ying HQ, He BS, Pan YQ, Deng QW, Sun HL, Chen J, Liu X, Wang SK. Up-regulated lncRNA-UCA1 contributes to progression of hepatocellular carcinoma through inhibition of miR-216b and activation of FGFR1/ERK signaling pathway. Oncotarget. 2015; 6:7899-7917. doi: 10.18632/oncotarget.3219.
23. Liu B, Sun L, Liu Q, Gong C, Yao Y, Lv X, Lin L, Yao H, Su F, Li D, Zeng M, Song E. A cytoplasmic NF-κB interacting long noncoding RNA blocks IκB phosphorylation and suppresses breast cancer metastasis. Cancer Cell. 2015; 27:370-381.
24. Richards EJ, Zhang G, Li ZP, Permuth-Wey J, Challa S, Li Y, Kong W, Dan S, Bui MM, Coppola D, Mao WM, Sellers TA, Cheng JQ. Long Non-coding RNAs (LncRNA) Regulated by Transforming Growth Factor (TGF) β: J Biol Chem. 2015;290:6857-6867.
25. Prensner JR, Zhao S, Erho N, Schipper M, Iyer MK, Dhanasekaran SM, Magi-Galluzzi C, Mehra R, Sahu A, Siddiqui J, Davicioni E, Den RB, Dicker AP, et al. RNA biomarkers associated with metastatic progression in prostate cancer: a multi-institutional high-throughput analysis of SChLAP1. Lancet Oncol. 2014; 15: 1469-1480.
26. Yang F, Huo XS, Yuan SX, Zhang L, Zhou WP, Wang F, Sun SH. Repression of the long noncoding RNA-LET by histone deacetylase 3 contributes to hypoxia-mediated metastasis. Mol Cell. 2013;49:1083-1096.
27. Beltran M, Puig I, Peña C, García JM, Alvarez AB, Peña R, Bonilla F, de Herreros AG. A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition. Genes Dev. 2008;22:756-769.
28. Deng Q, He B, Gao T, Pan Y, Sun H, Xu Y, Li R, Ying H, Wang F, Liu X, Chen J, Wang S. Up-regulation of 91H promotes tumor metastasis and predicts poor prognosis for patients with colorectal cancer. PLoS One. 2014; 9: e103022.
29. Gao T, He B, Pan Y, Xu Y, Li R, Deng Q, Sun H, Wang S. Long non-coding RNA 91H contributes to the occurrence and progression of esophageal squamous cell carcinoma by inhibiting IGF2 expression. Mol Carcinog. 2015; 54: 359-367.
30. Quagliata L, Matter MS, Piscuoglio S, Arabi L, Ruiz C, Procino A, Kovac M, Moretti F, Makowska Z, Boldanova T, Andersen JB, Hämmerle M, Tornillo L, et al. Long noncoding RNA HOTTIP/HOXA13 expression is associated with disease progression and predicts outcome in hepatocellular carcinoma patients. Hepatology. 2014;59: 911-923.
31. He W, Cai Q, Sun F, Zhong G, Wang P, Liu H, Luo J, Yu H, Huang J, Lin T. linc-UBC1 physically associates with polycomb repressive complex 2 (PRC2) and acts as a negative prognostic factor for lymph node metastasis and survival in bladder cancer. Biochim Biophys Acta. 2013;1832:1528-1537.
32. Li T, Xie J, Shen C, Cheng D, Shi Y, Wu Z, Deng X, Chen H, Shen B, Peng C, Li H, Zhan Q, Zhu Z. Upregulation of long noncoding RNA ZEB1-AS1 promotes tumor metastasis and predicts poor prognosis in hepatocellular carcinoma. Oncogene. 2015.
33. Matouk IJ, Raveh E, Abu-lail R, Mezan S, Gilon M, Gershtain E, Birman T, Gallula J, Schneider T, Barkali M, Richler C, Fellig Y, Sorin V, et al. Oncofetal H19 RNA promotes tumor metastasis. Biochim Biophys Acta 2014; 1843:1414-1426.
34. Xue G, Restuccia DF, Lan Q, Hynx D, Dirnhofer S, Hess D, Rüegg C, Hemmings BA. Akt/PKB-mediated phosphorylation of Twist1 promotes tumor metastasis via mediating cross-talk between PI3K/Akt and TGF-β signaling axes. Cancer Discov. 2012; 2:248-259.
35. Huber MA, Azoitei N, Baumann B, Grünert S, Sommer A, Pehamberger H, Kraut N, Beug H, Wirth T. NF-kappaB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression. J Clin Invest. 2004; 114:569-581.
36. Jechlinger M, Sommer A, Moriggl R, Seither P, Kraut N, Capodiecci P, Donovan M, Cordon-Cardo C, Beug H, Grünert S. Autocrine PDGFR signaling promotes mammary cancer metastasis. J Clin Invest. 2006;116:1561-1570.
37. Voutilainen R, Ilvesmäki V, Ariel I, Rachmilewitz J, de Groot N, Hochberg A. Parallel regulation of parentally imprinted H19 and insulin-like growth factor-II genes in cultured human fetal adrenal cells. Endocrinology. 1994; 134: 2051-2056.
38. Adriaenssens E, Lottin S, Berteaux N, Hornez L, Fauquette W, Fafeur V, Peyrat JP, Le Bourhis X, Hondermarck H, Coll J, Dugimont T, Curgy JJ. Cross-talk between mesenchyme and epithelium increases H19 gene expression during scattering and morphogenesis of epithelial cells. Exp Cell Res. 2002;275:215-229.
39. Montesano R, Matsumoto K, Nakamura T, Orci L. Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor. Cell. 1991 Nov 29;67(5):901-8.
40. Grotegut S, von Schweinitz D, Christofori G, Lehembre F. Hepatocyte growth factor induces cell scattering through MAPK/Egr-1-mediated up-regulation of Snail. EMBO J. 2006;25:3534-3545.
41. Arumugam T, Ramachandran V, Fournier KF, Wang H, Marquis L, Abbruzzese JL, Gallick GE, Logsdon CD, McConkey DJ, Choi W. Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer. Cancer Res. 2009;69:5820-5828.
42. Kajita M, McClinic KN, Wade PA. Aberrant expression of the transcription factors snail and slug alters the response to genotoxic stress. Mol Cell Biol. 2004; 24: 7559-7566.
43. Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene. 2010; 29: 4741-4751.
44. Saxena M, Stephens M A, Pathak H, Rangarajan A. Transcription factors that mediate epithelial-mesenchymal transition lead to multidrug resistance by up-regulating ABC transporters. Cell Death and Disease. 2011; 2: e179.
45. Doyle LA, Yang W, Rishi AK, Gao Y, Ross DD. H19 gene overexpression in atypical multidrug-resistant cells associated with expression of a 95-kilodalton membrane glycoprotein. Cancer Res. 1996; 56: 2904-2907.
46. Tsang WP, Kwok TT. Riboregulator H19 induction of MDR1-associated drug resistance in human hepatocellular carcinoma cells. Oncogene. 2007; 26: 4877-4881.
47. Matouk IJ, Mezan S, Mizrahi A, Ohana P, Abu-Lail R, Fellig Y, Degroot N, Galun E, Hochberg A. The oncofetal H19 RNA connection: hypoxia, p53 and cancer. Biochim Biophys Acta 2010; 1803: 443-451.
48. Sermeus A, and Michiels C. Reciprocal influence of the p53 and the hypoxic pathways, Cell Death and Disease. 2011; 2: e164.
49. Kim CY, Tsai MH, Osmanian C, Graeber TG, Lee JE, Giffard RG, DiPaolo JA, Peehl DM, Giaccia AJ. Selection of human cervical epithelial cells that possess reduced apoptotic potential to low-oxygen conditions. Cancer Res. 1997;57:4200-4204.
50. Koshikawa N, Maejima C, Miyazaki K, Nakagawara A, Takenaga K. Hypoxia selects for high-metastatic Lewis lung carcinoma cells overexpressing Mcl-1 and exhibiting reduced apoptotic potential in solid tumors. Oncogene. 2006 Feb 9;25(6):917-28.
51. Graeber TG, Osmanian C, Jacks T, Housman DE, Koch CJ, Lowe SW, Giaccia AJ. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature. 1996;379:88-91.
52. Matouk IJ, DeGroot N, Mezan S, Ayesh S, Abu-lail R, Hochberg A, Galun E. The H19 non-coding RNA is essential for human tumor growth. PLoS One 2007; 2:e845.
53. Ayesh S, Matouk I, Schneider T, Ohana P, Laster M, Al-Sharef W, De-Groot N, Hochberg A. Possible physiological role of H19 RNA. Mol Carcinog. 2002; 35: 63-74.
54. Whelan KA, Caldwell SA, Shahriari KS, Jackson SR, Franchetti LD, Johannes GJ, Reginato MJ. Hypoxia suppression of Bim and Bmf blocks anoikis and luminal clearing during mammary morphogenesis. Mol Biol Cell. 2010; 21:3829-3837.
55. Sullivan R, Graham CH. Hypoxia-driven selection of the metastatic phenotype. Cancer Metast Rev. 2007; 26:319-331.
56. Jo M, Lester RD, Montel V, Eastman B, Takimoto S, Gonias SL. Reversibility of epithelial-mesenchymal transition (EMT) induced in breast cancer cells by activation of urokinase receptor-dependent cell signaling. J Biol Chem. 2009; 284:22825-22833.
57. Shi Y, Wang Y, Luan W, Wang P, Tao T, Zhang J, Qian J, Liu N, You Y. Long non-coding RNA H19 promotes glioma cell invasion by deriving miR-675. PLoS One. 2014;23: e86295.
58. Andreeva AV, Kutuzov MA. Cadherin 13 in cancer. Genes Chromosomes Cancer. 2010; 49: 775-790.
59. Thuault S, Valcourt U, Petersen M, Manfioletti G, Heldin CH, Moustakas A. Transforming growth factorbeta employs HMGA2 to elicit epithelial-mesenchymal transition. J Cell Biol. 2006;174: 175-183.
60. Thuault S, Tan EJ, Peinado H, Cano A, Heldin CH, Moustakas A. HMGA2 and Smads co-regulate SNAIL1 expression during induction of epithelial-to-mesenchymal transition. J Biol Chem. 2008;283: 33437-33446.
61. Watanabe S, Ueda Y, Akaboshi S, Hino Y, Sekita Y, Nakao M. HMGA2 maintains oncogenic RAS-induced epithelialmesenchymal transition in human pancreatic cancer cells. Am J Pathol. 2009;174:854-868.
62. Mayr C, Hemann MT, Bartel DP. Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science. 2007; 315:1576-1579.
63. Lee YS, Dutta A. The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev.2007; 21: 1025-1030.
64. Kallen AN, Zhou XB, Xu J, Qiao C, Ma J, Yan L, Lu L, Liu C, Yi JS, Zhang H, Min W, Bennett AM, Gregory RI, Ding Y, Huang Y: The imprinted H19 lncRNA antagonizes let-7 microRNAs. Mol Cell. 2013; 52: 101-112.
65. Yan L, Zhou J, Gao Y, Ghazal S, Lu L, Bellone S, Yang Y, Liu N, Zhao X, Santin AD, Taylor H, Huang Y. Regulation of tumor cell migration and invasion by the H19/let-7 axis is antagonized by metformin-induced DNA methylation. Oncogene. 2014; Aug 4;0.
66. Matouk IJ, Halle D, Gilon M, Hochberg A. The noncoding RNAs of the H19-IGF2 imprinted loci: A focus on biological roles and therapeutic potential in Lung Cancer. J Transl Med. 2015; 13: 113.
67. Kaneko S, Li G, Son J, Xu C.F., Margueron R, Neubert T.A, Reinberg D. Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA. Genes Dev. 2010; 24:2615-2620.
68. Wang C, Liu X, Chen Z, Huang H, Jin Y, Kolokythas A, Wang A, Dai Y, Wong D.T, Zhou X. Polycomb group protein EZH2-mediated E-cadherin repression promotes metastasis of oral tongue squamous cell carcinoma. Mol Carcinogen. 2013;52:229-236.
69. Liu L, Xu Z, Zhong L, Wang H, Jiang S, Long Q, Xu J, Guo J. EZH2 promotes tumor cell migration and invasion via epigenetic repression of E-cadherin in renal cell carcinoma. BJU Int. 2014; 10.1111/bju.12702.
70. Tiwari N, Tiwari VK, Waldmeier L, Balwierz PJ, Arnold P, Pachkov M, Meyer-Schaller N, Schübeler D, van Nimwegen E, Christofori G. Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming. Cancer Cell. 2013; 10: 768-783.
71. Chen H, Tu S.W, Hsieh J.T. Down-regulation of human DAB2IP gene expression mediated by polycomb Ezh2 complex and histone deacetylase in prostate cancer. J Biol Chem. 2005; 280: 22437-22444.
72. Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA, Ghosh D, Sewalt RG, Otte AP, Hayes DF, Sabel MS, Livant D, Weiss SJ, Rubin MA, Chinnaiyan AM. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci USA. 2003; 100:11606-11611.
73. Monnier P, Martinet C, Pontis J, Stancheva I, Ait-Si-Ali S, Dandolo L. H19 lncRNA controls gene expression of the Imprinted Gene Network by recruiting MBD1. Proc Natl Acad Sci U S A. 2013;110:20693-20698.
74. Yoshimizu T, Miroglio A, Ripoche MA, Gabory A, Vernucci M, Riccio A, Colnot S, Godard C, Terris B, Jammes H, Dandolo L. The H19 locus acts in vivo as a tumor suppressor. Proc Natl Acad Sci U S A. 2008;105:12417-12422.
75. He D, Wang J, Zhang C, Shan B, Deng X, Li B, Zhou Y, Chen W, Hong J, Gao Y, Chen Z, Duan C. Down-regulation of miR-675-5p contributes to tumor progression and development by targeting pro-tumorigenic GPR55 in nonsmall cell lung cancer. Mol Cancer. 2015;14:73.
76. Tsang WP, Ng EK, Ng SS, Jin H, Yu J, Sung JJ, Kwok TT. Oncofetal H19-derived miR-675 regulates tumor suppressor RB in human colorectal cancer. Carcinogenesis. 2010;31:350-358.
77. Zhang L, Yang F, Yuan JH, Yuan SX, Zhou WP, Huo XS, Xu D, Bi HS, Wang F, Sun SH. Epigenetic activation of the MiR-200 family contributes to H19-mediated metastasis suppression in hepatocellular carcinoma. Carcinogenesis. 2013; 34:577-586.
78. Burk U, Schubert J, Wellner U, Schmalhofer O, Vincan E, Spaderna S, Brabletz T. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep. 2008;9:582-589.
79. Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y, Goodall GJ. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008;10:593-601.
80. Shimono Y, Zabala M, Cho RW, Lobo N, Dalerba P, Qian D, Diehn M, Liu H, Panula SP, Chiao E, Dirbas FM, Somlo G, Pera RA, Lao K, Clarke MF. Down-regulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell. 2009;138: 592-603.
81. Hernandez JM, Elahi A, Clark CW, Wang J, Humphries LA, Centeno B, Bloom G, Fuchs BC, Yeatman T, Shibata D. miR-675 mediates down-regulation of Twist1 and Rb in AFP-secreting hepatocellular carcinoma. Ann Surg Oncol. 2013;20:S625-635.
82. Yao D, Dai C, Peng S. Mechanism of the mesenchymalepithelial transition and its relationship with metastatic tumor formation. Mol Cancer Res. 2011;9:1608-1620.
83. Dykxhoorn DM, Wu Y, Xie H, Yu F, Lal A, Petrocca F, Martinvalet D, Song E, Lim B, Lieberman J. miR-200 enhances mouse breast cancer cell colonization to form distant metastases. PLoS One. 2009;4:e7181.
84. Liu YN, Yin JJ, Abou-Kheir W, Hynes PG, Casey OM, Fang L, Yi M, Stephens RM, Seng V, Sheppard-Tillman H, Martin P, Kelly K. MiR-1 and miR-200 inhibit EMT via Slug-dependent and tumorigenesis via Slug-independent mechanisms. Oncogene. 2013;32:296-306.
85. Brabletz T. To differentiate or not-routes towards metastasis. Nat Rev Cancer. 2012;12: 425-436.
86. Wang SP, Wang WL, Chang YL, Wu CT, Chao YC, Kao SH, Yuan A, Lin CW, Yang SC, Chan WK, Li KC, Hong TM, Yang PC. p53 controls cancer cell invasion by inducing the MDM2-mediated degradation of Slug. Nat Cell Biol. 2009;11: 694-704.
87. Dugimont T, Montpellier C, Adriaenssens E, Lottin S, Dumont L, Iotsova V, Lagrou C, Stéhelin D, Coll J, Curgy JJ. The H19 TATA-less promoter is efficiently repressed by wild-type tumor suppressor gene product p53. Oncogene. 1998; 16: 2395-2401.
88. Kim T, Veronese A, Pichiorri F, Lee TJ, Jeon YJ, Volinia S, Pineau P, Marchio A, Palatini J, Suh SS, Alder H, Liu CG, Dejean A, Croce CM. p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2. J Exp Med. 2011;208:875-883.
89. Bauderlique-Le Roy H, Vennin C, Brocqueville G, Spruyt N, Adriaenssens E, Bourette RP. Enrichment of Human Stem-Like Prostate Cells with s-SHIP Promoter Activity Uncovers a Role in Stemness for the Long Noncoding RNA H19. Stem Cells Dev. 2015;24: 1252-1262.
90. Huang Y, Zheng Y, Jia L, Li W. Long Non-Coding RNA H19 Promotes Osteoblast Differentiation via TGF-β1/Smad3/HDAC Signaling pathway by Deriving miR-675. Stem Cells. 2015.
91. Dey BK, Pfeifer K, Dutta A. The H19 long noncoding RNA gives rise to microRNAs miR-675-3p and miR-675-5p to promote skeletal muscle differentiation and regeneration. Genes Dev. 2014;28: 491-501.
92. Jiang X, Yan Y, Hu M, Chen X, Wang Y, Dai Y, Wu D, Wang Y, Zhuang Z, Xia H. Increased level of H19 long noncoding RNA promotes invasion, angiogenesis, and stemness of glioblastoma cells. J Neurosurg. 2015; 14:1-8.
93. Matouk I, Raveh E, Ohana P, Lail RA, Gershtain E, Gilon M, De Groot N, Czerniak A, Hochberg A. The increasing complexity of the oncofetal h19 gene locus: functional dissection and therapeutic intervention. Int J Mol Sci. 2013;14: 4298-4316.
94. Sher N, Von Stetina JR, Bell GW, Matsuura S, Ravid K, Orr-Weaver TL. Fundamental differences in endoreplication in mammals and Drosophila revealed by analysis of endocycling and endomitotic cells. Proc Natl Acad Sci U S A. 2013;110: 9368-9373.
95. Rachmilewitz J, Gileadi O, Eldar-Geva T, Schneider T, de-Groot N, Hochberg A. Transcription of the H19 gene in differentiating cytotrophoblasts from human placenta. Mol Reprod Dev. 1992;32:196-202.
96. Poirier F, Chan CT, Timmons PM, Robertson EJ, Evans MJ, Rigby PW. The murine H19 gene is activated during embryonic stem cell differentiation in vitro and at the time of implantation in the developing embryo. Development. 1991;113:1105-1114.
97. Li GQ, Zhang Y, Liu D, Qian YY, Zhang H, Guo SY, Sunagawa M, Hisamitsu T, Liu YQ. PI3 kinase/Akt/HIF-1a pathway is associated with hypoxia-induced epithelialmesenchymal transition in fibroblast-like synoviocytes of rheumatoid arthritis. Mol Cell Biochem. 2013;372:221-231.
98. Stuhlmüller B, Kunisch E, Franz J, Martinez-Gamboa L, Hernandez MM, Pruss A, Ulbrich N, Erdmann VA, Burmester GR, Kinne RW. Detection of oncofetal h19 RNA in rheumatoid arthritis synovial tissue. Am J Pathol. 2003;163:901-911.
99. Matouk IJ, Ohana P, Galun E, deGroot N, Hochberg A. The pivotal role of the oncofetal H19 RNA in human cancer, a new hope. Gene therapy and cancer research focus. 2008; 240-261.
100. Fellig Y, Ariel I, Ohana P, Schachter P, Sinelnikov I, Birman T, Ayesh S, Schneider T, de Groot N, Czerniak A, Hochberg A. H19 expression in hepatic metastases from a range of human carcinomas. J Clin Pathol. 2005;58:1064-1068.
101. Dugimont T, Curgy JJ, Wernert N, Delobelle A, Raes MB, Joubel A, Stehelin D, Coll J. The H19 gene is expressed within both epithelial and stromal components of human invasive adenocarcinomas. Biol Cell. 1995;85:117-124.
102. Sorin V, Mizrahi A, Ohana P, Ayesh S, Birman T, Hochberg A, and Czerniak A. Partial Hepatectomy in rats results in significant growth of liver metastases by increased expression of H19 gene. Cancer Therapy. 2009; 7: 240-244.
103. Yoshimura H, Matsuda Y, Suzuki T, Naito Z, Ishiwata T. Long noncoding rna h19 as a novel therapeutic target for pancreatic cancer. Cancer Research.2014; 74: 5203-5203.
104. Amit D, Matouk IJ, Lavon I, Birman T, Galula J, Abu-Lail R, Schneider T, Siegal T, Hochberg A, Fellig Y. Transcriptional targeting of glioblastoma by diphtheria toxin-A driven by both H19 and IGF2-P4 promoters. Int J Clin Exp Med. 2012;5:124-135.
105. Davis FM, Stewart TA, Thompson EW, Monteith GR. Targeting EMT in cancer: opportunities for pharmacological intervention. Trends Pharmacol Sci. 2014;35:479-488.
106. Sidi AA, Ohana P, Benjamin S, Shalev M, Ransom JH, Lamm D, Hochberg A, Leibovitch I. 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: 2379-2383.
107. Mizrahi A, Czerniak A, Ohana P, Amiur S, Gallula J, Matouk I, Abu-Lail R, Birman T, Hochberg A, Levy T. Treatment of ovarian cancer ascites by intra-peritoneal injection of diphtheria toxin A chain-H19 vector: a case report. J Med Case Rep. 2010 27;4:228.
108. Sorin V, Ohana P, Mizrahi A, Matouk I, Birman T, Hochberg A, Czerniak A. Regional therapy with DTA-H19 vector suppresses growth of colon adenocarcinoma metastases in the rat liver. Int J Oncol 2011; 39: 1407-1412.
109. Ohana P, Schachter P, Ayesh B, Mizrahi A, Birman T, Schneider T, Matouk I, Ayesh S, Kuppen PJ, de Groot N, Czerniak A, Hochberg A. Regulatory sequences of H19 and IGF2 genes in DNA-based therapy of colorectal rat liver metastases. J Gene Med. 2005;7: 366-374.
110. Schlag PM, Benhidjeb T, Stroszczynski C. Resection and local therapy for liver metastases. Best Pract Res Clin Gastroenterol. 2002; 16: 299-317.
111. Sorin V, Ohana P, Gallula J, Birman T, Matouk I, Hubert A, Gilon M, Hochberg A, Czerniak A. H19-promoter-targeted therapy combined with gemcitabine in the treatment of pancreatic cancer. ISRN Oncol. 2012;2012:351750.