LncRNA HULC enhances epithelial-mesenchymal transition to promote tumorigenesis and metastasis of hepatocellular carcinoma via the miR-200a-3p/ZEB1 signaling pathway

Oncotarget

Volumn 7, Issue 27, 2016, Pages 42431-42446

  Li, Shi Peng ^a   Xu, Hai Xu ^a   Yu, Yao ^a   He, Jin Dan ^a   Wang, Zhen ^a   Xu, Yan Jie ^a   Wang, Chang Ying ^a   Zhang, Hai Ming ^a,b   Zhang, Rong Xin ^a   Zhang, Jian Jun ^a,b   Yao, Zhi ^a   Shen, Zhong Yang ^a,b  

^a TIANJIN MEDICAL UNIVERSITY   (China)

^b TIANJIN FIRST CENTRAL HOSPITAL   (China)

Author keywords

Epithelial mesenchymal transition; Hepatocellular carcinoma; LncRNA HULC; MiR 200a 3p; ZEB1

Indexed keywords

ACETYLCYSTEINE; HULC LONG NON-CODING RNA, HUMAN; LONG UNTRANSLATED RNA; MICRORNA; MIRN200 MICRORNA, HUMAN; SMALL INTERFERING RNA; TRANSCRIPTION FACTOR ZEB1; ZEB1 PROTEIN, HUMAN;

AGED; ANIMAL; APOPTOSIS; BAGG ALBINO MOUSE; CANCER TRANSPLANTATION; CARCINOGENESIS; CELL PROLIFERATION; CELL TRANSFORMATION; DISEASE EXACERBATION; EPITHELIAL MESENCHYMAL TRANSITION; FEMALE; GENETICS; HUMAN; LENTIVIRUS; LIVER; LIVER CELL CARCINOMA; LIVER TUMOR; MALE; METABOLISM; METASTASIS; MIDDLE AGED; MOUSE; NUDE MOUSE; SIGNAL TRANSDUCTION;

ACETYLCYSTEINE; AGED; ANIMALS; APOPTOSIS; CARCINOGENESIS; CARCINOMA, HEPATOCELLULAR; CELL PROLIFERATION; CELL TRANSFORMATION, NEOPLASTIC; DISEASE PROGRESSION; EPITHELIAL-MESENCHYMAL TRANSITION; FEMALE; HUMANS; LENTIVIRUS; LIVER; LIVER NEOPLASMS; MALE; MICE; MICE, INBRED BALB C; MICE, NUDE; MICRORNAS; MIDDLE AGED; NEOPLASM METASTASIS; NEOPLASM TRANSPLANTATION; RNA, LONG NONCODING; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; ZINC FINGER E-BOX-BINDING HOMEOBOX 1;

EID: 84983429011     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.9883     Document Type: Article

References (50)

1. 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.
2. Panzitt K, Tschernatsch MM, Guelly C, Moustafa T, Stradner M, Strohmaier HM, Buck CR, Denk H, Schroeder R, Trauner M, Zatloukal K. Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. GASTROENTEROLOGY. 2007; 132:330-342.
3. Vinciguerra M. Protein intake, chronic liver diseases, and hepatocellular carcinoma. HEPATOLOGY. 2015; 61:730.
4. Zhang F, Zhang L, Zhang C. Long noncoding RNAs and tumorigenesis: genetic associations, molecular mechanisms, and therapeutic strategies. Tumour Biol. 2016; 37:163-175. doi: 10.1007/s13277-015-4445-4.
5. Smolle MA, Bullock MD, Ling H, Pichler M, Haybaeck J. Long Non-Coding RNAs in Endometrial Carcinoma. INT J MOL SCI. 2015; 16:26463-26472.
6. Aune TM, Crooke PR, Spurlock CR. Long noncoding RNAs in T lymphocytes. J Leukoc Biol. 2016; 99:31-44. doi: 10.1189/jlb.1RI0815-389R.
7. Zhao J, Greene CM, Gray SG, Lawless MW. Long noncoding RNAs in liver cancer: what we know in 2014. Expert Opin Ther Targets. 2014; 18:1207-1218.
8. Sun J, Bie B, Zhang S, Yang J, Li Z. Long non-coding RNAs: critical players in hepatocellular carcinoma. INT J MOL SCI. 2014; 15:20434-20448.
9. Wang GY, Zhu YY, Zhang YQ. The functional role of long non-coding RNA in digestive system carcinomas. Bull Cancer. 2014; 101:E27-E31.
10. Hammerle M, Gutschner T, Uckelmann H, Ozgur S, Fiskin E, Gross M, Skawran B, Geffers R, Longerich T, Breuhahn K, Schirmacher P, Stoecklin G, Diederichs S. Posttranscriptional destabilization of the liver-specific long noncoding RNA HULC by the IGF2 mRNA-binding protein 1 (IGF2BP1). HEPATOLOGY. 2013; 58:1703-1712.
11. Hammerle M, Gutschner T, Uckelmann H, Ozgur S, Fiskin E, Gross M, Skawran B, Geffers R, Longerich T, Breuhahn K, Schirmacher P, Stoecklin G, Diederichs S. Posttranscriptional destabilization of the liver-specific long noncoding RNA HULC by the IGF2 mRNA-binding protein 1 (IGF2BP1). HEPATOLOGY. 2013; 58:1703-1712.
12. Du Y, Kong G, You X, Zhang S, Zhang T, Gao Y, Ye L, Zhang X. Elevation of highly up-regulated in liver cancer (HULC) by hepatitis B virus X protein promotes hepatoma cell proliferation via down-regulating p18. J BIOL CHEM. 2012; 287:26302-26311.
13. Cui M, Xiao Z, Wang Y, Zheng M, Song T, Cai X, Sun B, Ye L, Zhang X. Long noncoding RNA HULC modulates abnormal lipid metabolism in hepatoma cells through an miR-9-mediated RXRA signaling pathway. CANCER RES. 2015; 75:846-857.
14. 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; 31:358-364.
15. Peng W, Gao W, Feng J. Long noncoding RNA HULC is a novel biomarker of poor prognosis in patients with pancreatic cancer. MED ONCOL. 2014; 31:346.
16. Akalay I, Janji B, Hasmim M, Noman MZ, Thiery JP, Mami-Chouaib F, Chouaib S. EMT impairs breast carcinoma cell susceptibility to CTL-mediated lysis through autophagy induction. AUTOPHAGY. 2013; 9:1104-1106.
17. Bottoni P, Isgro MA, Scatena R. The epithelialmesenchymal transition in cancer: a potential critical topic for translational proteomic research. Expert Rev Proteomics. 2015:1-19.
18. Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? CELL. 2011; 146:353-358.
19. Liang WC, Fu WM, Wong CW, Wang Y, Wang WM, Hu GX, Zhang L, Xiao LJ, Wan DC, Zhang JF, Waye MM. The lncRNA H19 promotes epithelial to mesenchymal transition by functioning as miRNA sponges in colorectal cancer. ONCOTARGET. 2015; 6:22513-22525. doi: 10.18632/ oncotarget.4154.
20. Saito T, Kurashige J, Nambara S, Komatsu H, Hirata H, Ueda M, Sakimura S, Uchi R, Takano Y, Shinden Y, Iguchi T, Eguchi H, Ehata S, Murakami K, Sugimachi K, Mimori K. A Long Non-coding RNA Activated by Transforming Growth Factor-beta is an Independent Prognostic Marker of Gastric Cancer. ANN SURG ONCOL. 2015; 22:S915-22. doi: 10.1245/s10434-015-4554-8.
21. Brabletz S, Brabletz T. The ZEB/miR-200 feedback loop-a motor of cellular plasticity in development and cancer? EMBO REP. 2010; 11:670-677.
22. Bracken CP, Gregory PA, Kolesnikoff N, Bert AG, Wang J, Shannon MF, Goodall GJ. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. CANCER RES. 2008; 68:7846-7854.
23. Vincent T, Neve EP, Johnson JR, Kukalev A, Rojo F, Albanell J, Pietras K, Virtanen I, Philipson L, Leopold PL, Crystal RG, de Herreros AG, Moustakas A, Pettersson RF, Fuxe J. A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelialmesenchymal transition. NAT CELL BIOL. 2009; 11:943-950.
24. Maass PG, Rump A, Schulz H, Stricker S, Schulze L, Platzer K, Aydin A, Tinschert S, Goldring MB, Luft FC, Bahring S. A misplaced lncRNA causes brachydactyly in humans. J CLIN INVEST. 2012; 122:3990-4002.
25. Jiang YJ, Bikle DD. LncRNA profiling reveals new mechanism for VDR protection against skin cancer formation. J Steroid Biochem Mol Biol. 2014; 144:87-90.
26. Yang Y, Li H, Hou S, Hu B, Liu J, Wang J. The noncoding RNA expression profile and the effect of lncRNA AK126698 on cisplatin resistance in non-small-cell lung cancer cell. PLOS ONE. 2013; 8:e65309.
27. Hu W, Yuan B, Flygare J, Lodish HF. Long noncoding RNA-mediated anti-apoptotic activity in murine erythroid terminal differentiation. Genes Dev. 2011; 25:2573-2578.
28. Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. NAT REV GENET. 2009; 10:155-159.
29. Yu FJ, Zheng JJ, Dong PH, Fan XM. Long non-coding RNAs and hepatocellular carcinoma. Mol Clin Oncol. 2015; 3:13-17.
30. Lv X, Li L, Lv L, Qu X, Jin S, Li K, Deng X, Cheng L, He H, Dong L. HOXD9 promotes epithelial-mesenchymal transition and cancer metastasis by ZEB1 regulation in hepatocellular carcinoma. J Exp Clin Cancer Res. 2015; 34:133.
31. Qi ST, Zhou J, Pan J, Zhang C, Silky C, Yan XR. Epithelial-mesenchymal transition and clinicopathological correlation in craniopharyngioma. HISTOPATHOLOGY. 2012; 61:711-725.
32. Oyanagi J, Ogawa T, Sato H, Higashi S, Miyazaki K. Epithelial-mesenchymal transition stimulates human cancer cells to extend microtubule-based invasive protrusions and suppresses cell growth in collagen gel. PLOS ONE. 2012; 7:e53209.
33. Fischer KR, Durrans A, Lee S, Sheng J, Li F, Wong ST, Choi H, El RT, Ryu S, Troeger J, Schwabe RF, Vahdat LT, Altorki NK, Mittal V, Gao D. Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. NATURE. 2015; 527:472-476. doi: 10.1038/nature15748.
34. Zheng X, Carstens JL, Kim J, Scheible M, Kaye J, Sugimoto H, Wu CC, LeBleu VS, Kalluri R. Epithelial-tomesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. NATURE. 2015; 527:525-530. doi: 10.1038/nature16064.
35. Stankic M, Pavlovic S, Chin Y, Brogi E, Padua D, Norton L, Massague J, Benezra R. TGF-beta-Id1 signaling opposes Twist1 and promotes metastatic colonization via a mesenchymal-to-epithelial transition. CELL REP. 2013; 5:1228-1242.
36. Gandhy SU, Imanirad P, Jin UH, Nair V, Hedrick E, Cheng Y, Corton JC, Kim K, Safe S. Specificity protein (Sp) transcription factors and metformin regulate expression of the long non-coding RNA HULC. ONCOTARGET. 2015; 6:26359-26372. doi: 10.18632/oncotarget.4560.
37. Chu PY, Hu FW, Yu CC, Tsai LL, Yu CH, Wu BC, Chen YW, Huang PI, Lo WL. Epithelial-mesenchymal transition transcription factor ZEB1/ZEB2 co-expression predicts poor prognosis and maintains tumor-initiating properties in head and neck cancer. ORAL ONCOL. 2013; 49:34-41.
38. Xiong H, Hong J, Du W, Lin YW, Ren LL, Wang YC, Su WY, Wang JL, Cui Y, Wang ZH, Fang JY. Roles of STAT3 and ZEB1 proteins in E-cadherin down-regulation and human colorectal cancer epithelial-mesenchymal transition. J BIOL CHEM. 2012; 287:5819-5832.
39. Yu JM, Sun W, Hua F, Xie J, Lin H, Zhou DD, Hu ZW. BCL6 induces EMT by promoting the ZEB1-mediated transcription repression of E-cadherin in breast cancer cells. CANCER LETT. 2015; 365:190-200.
40. Wellner U, Schubert J, Burk UC, Schmalhofer O, Zhu F, Sonntag A, Waldvogel B, Vannier C, Darling D, Zur HA, Brunton VG, Morton J, Sansom O, Schuler J, Stemmler MP, Herzberger C, et al. The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. NAT CELL BIOL. 2009; 11:1487-1495.
41. Schmalhofer O, Brabletz S, Brabletz T. E-cadherin, betacatenin, and ZEB1 in malignant progression of cancer. Cancer Metastasis Rev. 2009; 28:151-166.
42. Wei J, Zhang Y, Luo Y, Wang Z, Bi S, Song D, Dai Y, Wang T, Qiu L, Wen L, Yuan L, Yang JY. Aldose reductase regulates miR-200a-3p/141-3p to coordinate Keap1-Nrf2, Tgfbeta1/2, and Zeb1/2 signaling in renal mesangial cells and the renal cortex of diabetic mice. Free Radic Biol Med. 2014; 67:91-102.
43. 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.
44. Korpal M, Lee ES, Hu G, Kang Y. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J BIOL CHEM. 2008; 283:14910-14914.
45. Sun J, Ding W, Zhi J, Chen W. MiR-200 suppresses metastases of colorectal cancer through ZEB1. Tumour Biol. 2015.
46. Song X, Cao G, Jing L, Lin S, Wang X, Zhang J, Wang M, Liu W, Lv C. Analysing the relationship between lncRNA and protein-coding gene and the role of lncRNA as ceRNA in pulmonary fibrosis. J CELL MOL MED. 2014; 18:991-1003.
47. Cong N, Du P, Zhang A, Shen F, Su J, Pu P, Wang T, Zjang J, Kang C, Zhang Q. Downregulated microRNA- 200a promotes EMT and tumor growth through the wnt/ beta-catenin pathway by targeting the E-cadherin repressors ZEB1/ZEB2 in gastric adenocarcinoma. ONCOL REP. 2013; 29:1579-1587.
48. Saydam O, Shen Y, Wurdinger T, Senol O, Boke E, James MF, Tannous BA, Stemmer-Rachamimov AO, Yi M, Stephens RM, Fraefel C, Gusella JF, Krichevsky AM, Breakefield XO. Downregulated microRNA-200a in meningiomas promotes tumor growth by reducing E-cadherin and activating the Wnt/beta-catenin signaling pathway. MOL CELL BIOL. 2009; 29:5923-5940.
49. Nagaoka K, Zhang H, Watanabe G, Taya K. Epithelial cell differentiation regulated by MicroRNA-200a in mammary glands. PLOS ONE. 2013; 8:e65127.
50. Zhou JN, Zeng Q, Wang HY, Zhang B, Li ST, Nan X, Cao N, Fu CJ, Yan XL, Jia YL, Wang JX, Zhao AH, Li ZW, Li YH, Xie XY, Zhang XM, et al. MicroRNA- 125b attenuates epithelial-mesenchymal transitions and targets stem-like liver cancer cells through small mothers against decapentaplegic 2 and 4. HEPATOLOGY. 2015; 62:801-815.