Oncotarget

Research Papers:

EZH2 promotes cell migration and invasion but not alters cell proliferation by suppressing E-cadherin, partly through association with MALAT-1 in pancreatic cancer

Ting Han, Feng Jiao, Hai Hu, Cuncun Yuan, Lei Wang, Zi-Liang Jin, Weifeng Song and Li-Wei Wang _

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Oncotarget. 2016; 7:11194-11207. https://doi.org/10.18632/oncotarget.7156

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Abstract

Ting Han1,2,*, Feng Jiao1,2,*, Hai Hu1,*, Cuncun Yuan3, Lei Wang2, Zi-Liang Jin2, Wei-feng Song1, Li-Wei Wang1,2

1Department of Medical Oncology and Pancreatic Cancer Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China

2Shanghai Key Laboratory of Pancreatic Diseases, Shanghai 201620, China

3Department of Pathology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China

*Ting Han, Feng Jiao and Hai Hu contributed equally to this work and should be regarded as joint first authors

Correspondence to:

Li-Wei Wang, e-mail: yzwlw@hotmail.com

Feng Jiao, e-mail: jiao_f@outlook.com

Keywords: pancreatic cancer, enhancer of zeste homolog 2, metastasis associated lung adenocarcinoma transcript 1, long non-coding RNA, cell migration

Received: September 05, 2015    Accepted: January 23, 2016    Published: February 03, 2016

ABSTRACT

Enhancer of zeste homolog 2 (EZH2) is an essential component of the polycomb repressive complex 2 (PRC2), which is required for epigenetic silencing of target genes, including those affecting cancer progression. Its role in pancreatic cancer remains to be clarified; therefore, we investigated the effects of aberrantly expressed EZH2 on pancreatic cancer. We found that EZH2 expression is up-regulated in pancreatic cancer tissues and positively correlated with lymph node metastasis and advanced clinical stage in pancreatic cancer patients. EZH2 knockdown in pancreatic cancer cell lines inhibited cell migration and invasion, but did not alter cell proliferation. Silencing of EZH2 also increased E-cadherin expression in vitro, and E-cadherin expression was inversely correlated with EZH2 expression in pancreatic cancer tissue samples. Patients with high EZH2 and low E-cadherin expression had the worst prognosis. RIP and ChIP assays suggest that EZH2 is recruited to the E-cadherin promoter by the long non-coding RNA, MALAT-1 (metastasis associated in lung adenocarcinoma transcript 1), where it represses E-cadherin expression. Our results show that EZH2-based therapies may be an option for the treatment of pancreatic cancer.


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