Skip to main content
Top
Published in: Journal of Hematology & Oncology 1/2016

Open Access 01-12-2016 | Research

MicroRNA-26a suppresses epithelial-mesenchymal transition in human hepatocellular carcinoma by repressing enhancer of zeste homolog 2

Authors: De-Ning Ma, Zong-Tao Chai, Xiao-Dong Zhu, Ning Zhang, Di-Hua Zhan, Bo-Gen Ye, Cheng-Hao Wang, Cheng-Dong Qin, Yi-Ming Zhao, Wei-Ping Zhu, Man-Qing Cao, Dong-Mei Gao, Hui-Chuan Sun, Zhao-You Tang

Published in: Journal of Hematology & Oncology | Issue 1/2016

Login to get access

Abstract

Background

Our previous study reported that microRNA-26a (miR-26a) inhibited tumor progression by inhibiting tumor angiogenesis and intratumoral macrophage infiltration in hepatocellular carcinoma (HCC). The direct roles of miR-26a on tumor cell invasion remain poorly understood. In this study, we aim to explore the mechanism of miR-26a in modulating epithelial-mesenchymal transition (EMT) in HCC.

Methods

In vitro cell morphology and cell migration were compared between the hepatoma cell lines HCCLM3 and HepG2, which were established in the previous study. Overexpression and down-regulation of miR-26a were induced in these cell lines, and Western blot and immunofluorescence assays were used to detect the expression of EMT markers. Xenograft nude mouse models were used to observe tumor growth and pulmonary metastasis. Immunohistochemical assays were conducted to study the relationships between miR-26a expression and enhancer of zeste homolog 2 (EZH2) and E-cadherin expression in human HCC samples.

Results

Down-regulation of miR-26a in HCCLM3 and HepG2 cells resulted in an EMT-like cell morphology and high motility in vitro and increased in tumor growth and pulmonary metastasis in vivo. Through down-regulation of EZH2 expression and up-regulation of E-cadherin expression, miR-26a inhibited the EMT process in vitro and in vivo. Luciferase reporter assay showed that miR-26a directly interacted with EZH2 messenger RNA (mRNA). Furthermore, the expression of miR-26a was positively correlated with E-cadherin expression and inversely correlated with EZH2 expression in human HCC tissue.

Conclusions

miR-26a inhibited the EMT process in HCC by down-regulating EZH2 expression.
Literature
2.
go back to reference Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.CrossRefPubMed Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.CrossRefPubMed
3.
go back to reference Zhou XD, Tang ZY, Yang BH, Lin ZY, Ma ZC, Ye SL, et al. Experience of 1000 patients who underwent hepatectomy for small hepatocellular carcinoma. Cancer. 2001;91(8):1479–86.CrossRefPubMed Zhou XD, Tang ZY, Yang BH, Lin ZY, Ma ZC, Ye SL, et al. Experience of 1000 patients who underwent hepatectomy for small hepatocellular carcinoma. Cancer. 2001;91(8):1479–86.CrossRefPubMed
4.
go back to reference Waly RS, Yangde Z, Yuxiang C. Hepatocellular carcinoma: focus on different aspects of management. ISRN Oncol. 2012;2012:421673. Waly RS, Yangde Z, Yuxiang C. Hepatocellular carcinoma: focus on different aspects of management. ISRN Oncol. 2012;2012:421673.
5.
go back to reference Poon D, Anderson BO, Chen LT, Tanaka K, Lau WY, Van Cutsem E, et al. Management of hepatocellular carcinoma in Asia: consensus statement from the Asian Oncology Summit 2009. Lancet Oncol. 2009;10(11):1111–8.CrossRefPubMed Poon D, Anderson BO, Chen LT, Tanaka K, Lau WY, Van Cutsem E, et al. Management of hepatocellular carcinoma in Asia: consensus statement from the Asian Oncology Summit 2009. Lancet Oncol. 2009;10(11):1111–8.CrossRefPubMed
6.
go back to reference Tung-Ping PR, Fan ST, Wong J. Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg. 2000;232(1):10–24.CrossRef Tung-Ping PR, Fan ST, Wong J. Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg. 2000;232(1):10–24.CrossRef
7.
go back to reference van Zijl F, Zulehner G, Petz M, Schneller D, Kornauth C, Hau M, et al. Epithelial-mesenchymal transition in hepatocellular carcinoma. Future Oncol. 2009;5(8):1169–79.CrossRefPubMed van Zijl F, Zulehner G, Petz M, Schneller D, Kornauth C, Hau M, et al. Epithelial-mesenchymal transition in hepatocellular carcinoma. Future Oncol. 2009;5(8):1169–79.CrossRefPubMed
8.
go back to reference Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 2006;7(2):131–42.CrossRefPubMed Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 2006;7(2):131–42.CrossRefPubMed
9.
go back to reference Grunert S, Jechlinger M, Beug H. Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis. Nat Rev Mol Cell Biol. 2003;4(8):657–65.CrossRefPubMed Grunert S, Jechlinger M, Beug H. Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis. Nat Rev Mol Cell Biol. 2003;4(8):657–65.CrossRefPubMed
10.
go back to reference Perl AK, Wilgenbus P, Dahl U, Semb H, Christofori G. A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature. 1998;392(6672):190–3.CrossRefPubMed Perl AK, Wilgenbus P, Dahl U, Semb H, Christofori G. A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature. 1998;392(6672):190–3.CrossRefPubMed
11.
go back to reference Wells A, Yates C, Shepard CR. E-cadherin as an indicator of mesenchymal to epithelial reverting transitions during the metastatic seeding of disseminated carcinomas. Clin Exp Metastasis. 2008;25(6):621–8.CrossRefPubMedPubMedCentral Wells A, Yates C, Shepard CR. E-cadherin as an indicator of mesenchymal to epithelial reverting transitions during the metastatic seeding of disseminated carcinomas. Clin Exp Metastasis. 2008;25(6):621–8.CrossRefPubMedPubMedCentral
12.
go back to reference Sanchez-Tillo E, Liu Y, de Barrios O, Siles L, Fanlo L, Cuatrecasas M, et al. EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness. Cell Mol Life Sci. 2012;69(20):3429–56.CrossRefPubMed Sanchez-Tillo E, Liu Y, de Barrios O, Siles L, Fanlo L, Cuatrecasas M, et al. EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness. Cell Mol Life Sci. 2012;69(20):3429–56.CrossRefPubMed
13.
go back to reference Di LG, Garofalo M, Croce CM. MicroRNAs in cancer. Annu Rev Pathol. 2014;9:287–314.CrossRef Di LG, Garofalo M, Croce CM. MicroRNAs in cancer. Annu Rev Pathol. 2014;9:287–314.CrossRef
14.
go back to reference Chai ZT, Zhu XD, Ao JY, Wang WQ, Gao DM, Kong J, et al. microRNA-26a suppresses recruitment of macrophages by down-regulating macrophage colony-stimulating factor expression through the PI3K/Akt pathway in hepatocellular carcinoma. J Hematol Oncol. 2015;8(1):56.CrossRefPubMedPubMedCentral Chai ZT, Zhu XD, Ao JY, Wang WQ, Gao DM, Kong J, et al. microRNA-26a suppresses recruitment of macrophages by down-regulating macrophage colony-stimulating factor expression through the PI3K/Akt pathway in hepatocellular carcinoma. J Hematol Oncol. 2015;8(1):56.CrossRefPubMedPubMedCentral
15.
go back to reference Yang X, Zhang XF, Lu X, Jia HL, Liang L, Dong QZ, et al. MicroRNA-26a suppresses angiogenesis in human hepatocellular carcinoma by targeting hepatocyte growth factor-cMet pathway. Hepatology. 2014;59(5):1874–85.CrossRefPubMed Yang X, Zhang XF, Lu X, Jia HL, Liang L, Dong QZ, et al. MicroRNA-26a suppresses angiogenesis in human hepatocellular carcinoma by targeting hepatocyte growth factor-cMet pathway. Hepatology. 2014;59(5):1874–85.CrossRefPubMed
16.
go back to reference Yang X, Liang L, Zhang XF, Jia HL, Qin Y, Zhu XC, et al. MicroRNA-26a suppresses tumor growth and metastasis of human hepatocellular carcinoma by targeting interleukin-6-Stat3 pathway. Hepatology. 2013;58(1):158–70.CrossRefPubMed Yang X, Liang L, Zhang XF, Jia HL, Qin Y, Zhu XC, et al. MicroRNA-26a suppresses tumor growth and metastasis of human hepatocellular carcinoma by targeting interleukin-6-Stat3 pathway. Hepatology. 2013;58(1):158–70.CrossRefPubMed
17.
go back to reference Ji J, Shi J, Budhu A, Yu Z, Forgues M, Roessler S, et al. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med. 2009;361(15):1437–47.CrossRefPubMedPubMedCentral Ji J, Shi J, Budhu A, Yu Z, Forgues M, Roessler S, et al. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med. 2009;361(15):1437–47.CrossRefPubMedPubMedCentral
18.
go back to reference Chai ZT, Kong J, Zhu XD, Zhang YY, Lu L, Zhou JM, et al. MicroRNA-26a inhibits angiogenesis by down-regulating VEGFA through the PIK3C2alpha/Akt/HIF-1alpha pathway in hepatocellular carcinoma. PLoS One. 2013;8(10):e77957.CrossRefPubMedPubMedCentral Chai ZT, Kong J, Zhu XD, Zhang YY, Lu L, Zhou JM, et al. MicroRNA-26a inhibits angiogenesis by down-regulating VEGFA through the PIK3C2alpha/Akt/HIF-1alpha pathway in hepatocellular carcinoma. PLoS One. 2013;8(10):e77957.CrossRefPubMedPubMedCentral
19.
go back to reference Wang C, Liu X, Chen Z, Huang H, Jin Y, Kolokythas A, et al. Polycomb group protein EZH2-mediated E-cadherin repression promotes metastasis of oral tongue squamous cell carcinoma. Mol Carcinog. 2013;52(3):229–36.CrossRefPubMedPubMedCentral Wang C, Liu X, Chen Z, Huang H, Jin Y, Kolokythas A, et al. Polycomb group protein EZH2-mediated E-cadherin repression promotes metastasis of oral tongue squamous cell carcinoma. Mol Carcinog. 2013;52(3):229–36.CrossRefPubMedPubMedCentral
20.
go back to reference Takawa M, Masuda K, Kunizaki M, Daigo Y, Takagi K, Iwai Y, et al. Validation of the histone methyltransferase EZH2 as a therapeutic target for various types of human cancer and as a prognostic marker. Cancer Sci. 2011;102(7):1298–305.CrossRefPubMed Takawa M, Masuda K, Kunizaki M, Daigo Y, Takagi K, Iwai Y, et al. Validation of the histone methyltransferase EZH2 as a therapeutic target for various types of human cancer and as a prognostic marker. Cancer Sci. 2011;102(7):1298–305.CrossRefPubMed
21.
go back to reference Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG, et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature. 2002;419(6907):624–9.CrossRefPubMed Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG, et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature. 2002;419(6907):624–9.CrossRefPubMed
22.
go back to reference Gao SB, Xu B, Ding LH, Zheng QL, Zhang L, Zheng QF, et al. The functional and mechanistic relatedness of EZH2 and menin in hepatocellular carcinoma. J Hepatol. 2014;61(4):832–9.CrossRefPubMed Gao SB, Xu B, Ding LH, Zheng QL, Zhang L, Zheng QF, et al. The functional and mechanistic relatedness of EZH2 and menin in hepatocellular carcinoma. J Hepatol. 2014;61(4):832–9.CrossRefPubMed
23.
go back to reference Lu J, He ML, Wang L, Chen Y, Liu X, Dong Q, et al. MiR-26a inhibits cell growth and tumorigenesis of nasopharyngeal carcinoma through repression of EZH2. Cancer Res. 2011;71(1):225–33.CrossRefPubMed Lu J, He ML, Wang L, Chen Y, Liu X, Dong Q, et al. MiR-26a inhibits cell growth and tumorigenesis of nasopharyngeal carcinoma through repression of EZH2. Cancer Res. 2011;71(1):225–33.CrossRefPubMed
24.
go back to reference Yu L, Lu J, Zhang B, Liu X, Wang L, Li SY, et al. miR-26a inhibits invasion and metastasis of nasopharyngeal cancer by targeting EZH2. Oncol Lett. 2013;5(4):1223–8.PubMedPubMedCentral Yu L, Lu J, Zhang B, Liu X, Wang L, Li SY, et al. miR-26a inhibits invasion and metastasis of nasopharyngeal cancer by targeting EZH2. Oncol Lett. 2013;5(4):1223–8.PubMedPubMedCentral
25.
go back to reference Wu Y, Zhang L, Zhang L, Wang Y, Li H, Ren X, et al. Long non-coding RNA HOTAIR promotes tumor cell invasion and metastasis by recruiting EZH2 and repressing E-cadherin in oral squamous cell carcinoma. Int J Oncol. 2015;46(6):2586–94.PubMed Wu Y, Zhang L, Zhang L, Wang Y, Li H, Ren X, et al. Long non-coding RNA HOTAIR promotes tumor cell invasion and metastasis by recruiting EZH2 and repressing E-cadherin in oral squamous cell carcinoma. Int J Oncol. 2015;46(6):2586–94.PubMed
26.
go back to reference Zhang N, Wang L, Chai ZT, Zhu ZM, Zhu XD, Ma DN, et al. Incomplete radiofrequency ablation enhances invasiveness and metastasis of residual cancer of hepatocellular carcinoma cell HCCLM3 via activating beta-catenin signaling. PLoS One. 2014;9(12):e115949.CrossRefPubMedPubMedCentral Zhang N, Wang L, Chai ZT, Zhu ZM, Zhu XD, Ma DN, et al. Incomplete radiofrequency ablation enhances invasiveness and metastasis of residual cancer of hepatocellular carcinoma cell HCCLM3 via activating beta-catenin signaling. PLoS One. 2014;9(12):e115949.CrossRefPubMedPubMedCentral
27.
go back to reference Jansen MP, Reijm EA, Sieuwerts AM, Ruigrok-Ritstier K, Look MP, Rodriguez-Gonzalez FG, et al. High miR-26a and low CDC2 levels associate with decreased EZH2 expression and with favorable outcome on tamoxifen in metastatic breast cancer. Breast Cancer Res Treat. 2012;133(3):937–47.CrossRefPubMedPubMedCentral Jansen MP, Reijm EA, Sieuwerts AM, Ruigrok-Ritstier K, Look MP, Rodriguez-Gonzalez FG, et al. High miR-26a and low CDC2 levels associate with decreased EZH2 expression and with favorable outcome on tamoxifen in metastatic breast cancer. Breast Cancer Res Treat. 2012;133(3):937–47.CrossRefPubMedPubMedCentral
28.
go back to reference Zhang B, Liu XX, He JR, Zhou CX, Guo M, He M, et al. Pathologically decreased miR-26a antagonizes apoptosis and facilitates carcinogenesis by targeting MTDH and EZH2 in breast cancer. Carcinogenesis. 2011;32(1):2–9.CrossRefPubMed Zhang B, Liu XX, He JR, Zhou CX, Guo M, He M, et al. Pathologically decreased miR-26a antagonizes apoptosis and facilitates carcinogenesis by targeting MTDH and EZH2 in breast cancer. Carcinogenesis. 2011;32(1):2–9.CrossRefPubMed
29.
go back to reference Huse JT, Brennan C, Hambardzumyan D, Wee B, Pena J, Rouhanifard SH, et al. The PTEN-regulating microRNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivo. Genes Dev. 2009;23(11):1327–37.CrossRefPubMedPubMedCentral Huse JT, Brennan C, Hambardzumyan D, Wee B, Pena J, Rouhanifard SH, et al. The PTEN-regulating microRNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivo. Genes Dev. 2009;23(11):1327–37.CrossRefPubMedPubMedCentral
30.
31.
go back to reference Zou ZJ, Fan L, Wang L, Xu J, Zhang R, Tian T, et al. miR-26a and miR-214 down-regulate expression of the PTEN gene in chronic lymphocytic leukemia, but not PTEN mutation or promoter methylation. Oncotarget. 2015;6(2):1276–85.CrossRefPubMedPubMedCentral Zou ZJ, Fan L, Wang L, Xu J, Zhang R, Tian T, et al. miR-26a and miR-214 down-regulate expression of the PTEN gene in chronic lymphocytic leukemia, but not PTEN mutation or promoter methylation. Oncotarget. 2015;6(2):1276–85.CrossRefPubMedPubMedCentral
32.
33.
go back to reference Chang TC, Yu D, Lee YS, Wentzel EA, Arking DE, West KM, et al. Widespread microRNA repression by Myc contributes to tumorigenesis. Nat Genet. 2008;40(1):43–50.CrossRefPubMedPubMedCentral Chang TC, Yu D, Lee YS, Wentzel EA, Arking DE, West KM, et al. Widespread microRNA repression by Myc contributes to tumorigenesis. Nat Genet. 2008;40(1):43–50.CrossRefPubMedPubMedCentral
34.
go back to reference Ciarapica R, Russo G, Verginelli F, Raimondi L, Donfrancesco A, Rota R, et al. Deregulated expression of miR-26a and Ezh2 in rhabdomyosarcoma. Cell Cycle. 2009;8(1):172–5.CrossRefPubMed Ciarapica R, Russo G, Verginelli F, Raimondi L, Donfrancesco A, Rota R, et al. Deregulated expression of miR-26a and Ezh2 in rhabdomyosarcoma. Cell Cycle. 2009;8(1):172–5.CrossRefPubMed
35.
go back to reference Kota J, Chivukula RR, O’Donnell KA, Wentzel EA, Montgomery CL, Hwang HW, et al. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell. 2009;137(6):1005–17.CrossRefPubMedPubMedCentral Kota J, Chivukula RR, O’Donnell KA, Wentzel EA, Montgomery CL, Hwang HW, et al. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell. 2009;137(6):1005–17.CrossRefPubMedPubMedCentral
36.
go back to reference Steeg PS. Tumor metastasis: mechanistic insights and clinical challenges. Nat Med. 2006;12(8):895–904.CrossRefPubMed Steeg PS. Tumor metastasis: mechanistic insights and clinical challenges. Nat Med. 2006;12(8):895–904.CrossRefPubMed
37.
go back to reference Creighton CJ, Chang JC, Rosen JM. Epithelial-mesenchymal transition (EMT) in tumor-initiating cells and its clinical implications in breast cancer. J Mammary Gland Biol Neoplasia. 2010;15(2):253–60.CrossRefPubMed Creighton CJ, Chang JC, Rosen JM. Epithelial-mesenchymal transition (EMT) in tumor-initiating cells and its clinical implications in breast cancer. J Mammary Gland Biol Neoplasia. 2010;15(2):253–60.CrossRefPubMed
38.
go back to reference Gunasinghe NP, Wells A, Thompson EW, Hugo HJ. Mesenchymal-epithelial transition (MET) as a mechanism for metastatic colonisation in breast cancer. Cancer Metastasis Rev. 2012;31(3–4):469–78.CrossRefPubMed Gunasinghe NP, Wells A, Thompson EW, Hugo HJ. Mesenchymal-epithelial transition (MET) as a mechanism for metastatic colonisation in breast cancer. Cancer Metastasis Rev. 2012;31(3–4):469–78.CrossRefPubMed
39.
go back to reference Lee SJ, Kim KH, Park KK. Mechanisms of fibrogenesis in liver cirrhosis: the molecular aspects of epithelial-mesenchymal transition. World J Hepatol. 2014;6(4):207–16.CrossRefPubMedPubMedCentral Lee SJ, Kim KH, Park KK. Mechanisms of fibrogenesis in liver cirrhosis: the molecular aspects of epithelial-mesenchymal transition. World J Hepatol. 2014;6(4):207–16.CrossRefPubMedPubMedCentral
41.
go back to reference Korpal M, Kang Y. The emerging role of miR-200 family of microRNAs in epithelial-mesenchymal transition and cancer metastasis. RNA Biol. 2008;5(3):115–9.CrossRefPubMedPubMedCentral Korpal M, Kang Y. The emerging role of miR-200 family of microRNAs in epithelial-mesenchymal transition and cancer metastasis. RNA Biol. 2008;5(3):115–9.CrossRefPubMedPubMedCentral
42.
go back to reference Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008;10(5):593–601.CrossRefPubMed Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008;10(5):593–601.CrossRefPubMed
43.
go back to reference Alajez NM, Shi W, Hui AB, Bruce J, Lenarduzzi M, Ito E, et al. Enhancer of Zeste homolog 2 (EZH2) is overexpressed in recurrent nasopharyngeal carcinoma and is regulated by miR-26a, miR-101, and miR-98. Cell Death Dis. 2010;1:e85.CrossRefPubMedPubMedCentral Alajez NM, Shi W, Hui AB, Bruce J, Lenarduzzi M, Ito E, et al. Enhancer of Zeste homolog 2 (EZH2) is overexpressed in recurrent nasopharyngeal carcinoma and is regulated by miR-26a, miR-101, and miR-98. Cell Death Dis. 2010;1:e85.CrossRefPubMedPubMedCentral
44.
go back to reference Zhao H, Xu Y, Mao Y, Zhang Y. Effects of EZH2 gene on the growth and migration of hepatocellular carcinoma HepG2 cells. Hepatobiliary Surg Nutr. 2013;2(2):78–83.PubMedPubMedCentral Zhao H, Xu Y, Mao Y, Zhang Y. Effects of EZH2 gene on the growth and migration of hepatocellular carcinoma HepG2 cells. Hepatobiliary Surg Nutr. 2013;2(2):78–83.PubMedPubMedCentral
45.
go back to reference Sun NX, Ye C, Zhao Q, Zhang Q, Xu C, Wang SB, 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(7):e100340.CrossRefPubMedPubMedCentral Sun NX, Ye C, Zhao Q, Zhang Q, Xu C, Wang SB, 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(7):e100340.CrossRefPubMedPubMedCentral
46.
go back to reference Thompson EW, Newgreen DF, Tarin D. Carcinoma invasion and metastasis: a role for epithelial-mesenchymal transition. Cancer Res. 2005;65(14):5991–5. discussion 5995.CrossRefPubMed Thompson EW, Newgreen DF, Tarin D. Carcinoma invasion and metastasis: a role for epithelial-mesenchymal transition. Cancer Res. 2005;65(14):5991–5. discussion 5995.CrossRefPubMed
47.
go back to reference Li Y, Tang ZY, Ye SL, Liu YK, Chen J, Xue Q, et al. Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97. World J Gastroenterol. 2001;7(5):630–6.PubMedPubMedCentral Li Y, Tang ZY, Ye SL, Liu YK, Chen J, Xue Q, et al. Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97. World J Gastroenterol. 2001;7(5):630–6.PubMedPubMedCentral
48.
go back to reference Sun FX, Tang ZY, Lui KD, Ye SL, Xue Q, Gao DM, et al. Establishment of a metastatic model of human hepatocellular carcinoma in nude mice via orthotopic implantation of histologically intact tissues. Int J Cancer. 1996;66(2):239–43.CrossRefPubMed Sun FX, Tang ZY, Lui KD, Ye SL, Xue Q, Gao DM, et al. Establishment of a metastatic model of human hepatocellular carcinoma in nude mice via orthotopic implantation of histologically intact tissues. Int J Cancer. 1996;66(2):239–43.CrossRefPubMed
Metadata
Title
MicroRNA-26a suppresses epithelial-mesenchymal transition in human hepatocellular carcinoma by repressing enhancer of zeste homolog 2
Authors
De-Ning Ma
Zong-Tao Chai
Xiao-Dong Zhu
Ning Zhang
Di-Hua Zhan
Bo-Gen Ye
Cheng-Hao Wang
Cheng-Dong Qin
Yi-Ming Zhao
Wei-Ping Zhu
Man-Qing Cao
Dong-Mei Gao
Hui-Chuan Sun
Zhao-You Tang
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2016
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-015-0229-y

Other articles of this Issue 1/2016

Journal of Hematology & Oncology 1/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine