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 1, 2, * , Feng Jiao 1, 2, * , Hai Hu 1, * , Cuncun Yuan 3 , Lei Wang 2 , Zi-Liang Jin 2 , Wei-feng Song 1 , Li-Wei Wang 1, 2 1 Department of Medical Oncology and Pancreatic Cancer Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China 2 Shanghai Key Laboratory of Pancreatic Diseases, Shanghai 201620, China 3 Department 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.