LncRNA HOTAIR acts as competing endogenous RNA to control the expression of Notch3 via sponging miR-613 in pancreatic cancer

// Huihua Cai 1, * , Jie Yao 2, * , Yong An 1 , Xuemin Chen 1 , Weibo Chen 1 , Di Wu 1 , Boyang Luo 1 , Yong Yang 1 , Yong Jiang 1 , Donglin Sun 1 , Xiaozhou He 3 1 Department of Hepatobiliary Surgery, The First People's Hospital of Changzhou, The Third Hospital Affiliated to Soochow University, Changzhou, Jiangsu, China 2 Department of Hepatobiliary and Pancreatic Surgery, Northern Jiangsu People's Hospital, The Clinic Medical College of Yangzhou University, Yangzhou, Jiangsu, China 3 Department of Urology, The First People's Hospital of Changzhou, The Third Hospital Affiliated to Soochow University, Changzhou, Jiangsu, China * These authors contributed equally to this work Correspondence to: Xiaozhou He, email: chh20072077@sina.com Donglin Sun, email: czyysdl@163.com Keywords: pancreatic cancer, miR-613, HOTAIR, cell proliferation, invasion and migration Received: February 10, 2017      Accepted: March 11, 2017      Published: March 22, 2017 ABSTRACT Pancreatic cancer is one of the most deadly cancers with a poor prognosis. Though studies have implicated the roles of microRNAs in pancreatic cancer progression, little is known about the role of miR-613 in pancreatic cancer. In the present study, the expression of miR-613 was down-regulated in pancreatic cancer tissues and cancer cell lines. Down-regulation of miR-613 was positively correlated with tumor differentiation, advanced TNM stage, nodal metastasis and shorter overall survival in patients with pancreatic cancer. Overexpression of miR-613 suppressed cell proliferation, invasion and migration, and induced cell apoptosis and cell cycle arrest at G0/G1 phase in pancreatic cancer cells. Bioinformatics analysis, luciferase reporter assay and rescue experiments showed that notch3 was a direct target of miR-613. MiR-613 was inversely correlated with notch3 expression in pancreatic cancer tissues. The long non-coding RNA, HOX transcript antisense RNA (HOTAIR) was up-regulated in both pancreatic cancer tissues and cancer cell lines, and HOTAIR suppressed the expression of miR-613 via functioning as a competing endogenous RNA. In vivo studies showed that stable overexpression of miR-613 or knock-down of HOTAIR suppressed tumor growth and also reduced the expression of notch3. In conclusion, these results suggest that HOTAIR functions as a competing endogenous RNA to regulate notch3 expression via sponging miR-613 in pancreatic cancer.