miR-597-5p inhibits cell growth and promotes cell apoptosis by targeting ELK1 in pancreatic cancer

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RESEARCH ARTICLE

miR‑597‑5p inhibits cell growth and promotes cell apoptosis by targeting ELK1 in pancreatic cancer Shizong Li1 · Xianglu Li2   · Xuehua Xing2 · Lin Wang2 Received: 27 March 2020 / Accepted: 20 June 2020 © Japan Human Cell Society 2020

Abstract Pancreatic cancer is a malignant disease with poor prognosis. Emerging evidences have showed that miR-597-5p is closely related to tumor development. However, the functional roles of miR-597-5p in pancreatic cancer remain unknown. This study aimed to investigate the expression of miR-597-5p in pancreatic cancer tissues and cells, and explored its regulatory mechanism during pancreatic cancer progression. Pancreatic cancer and adjacent tissues were obtained to detect the expression of miR-597-5p by RT-qPCR. Cell growth, apoptosis, and related protein expression were, respectively, tested by CCK-8 assay, cell formation, wound healing, Transwell assay, flow cytometry, and western blotting. Finally, the pancreatic cancer mice model was constructed. In vitro and in vivo results showed that miR-597-5p expression was down-regulated in pancreatic cancer tissues and cell lines, and increased the overall survival of pancreatic cancer patients. Moreover, miR-597-5p decreased pancreatic cancer cell viability, reduced relative wound width, suppressed colony formation and decreased invasive cell number, as well as reduced the expression of proliferating cell nuclear antigen (PCNA), Ki67, Cyclin D1, N-cad, and Bcl-2. Meanwhile, it increased pancreatic cancer cell apoptosis and the expression of E-cad, cleaved caspase 3, and Bax. The dual-luciferase reporter assay confirmed miR-597-5p could directly target e-twenty six like-1 (ELK1) oncogene. The reduction of cell growth and the induction of cell apoptosis induced by miR-597-5p were reversed by ELK1. In addition, miR-597-5p inhibited the growth of pancreatic cancer in vivo. This study demonstrated that miR-597-5p may be a novel suppressor of pancreatic cancer. It inhibits pancreatic cancer cell growth and promotes apoptosis by the down-regulation of ELK1 in vitro and in vivo. Keywords  miR-597-5p · Pancreatic cancer · ELK1 · Apoptosis · Viability

Introduction Pancreatic cancer is a malignant gastrointestinal cancer with poor diagnosis [1]. The causes of pancreatic cancer may be related to smoking, alcohol consumption, high-fat and highprotein diets, environmental pollution, and genetic factors [2, 3]. The most common symptoms of pancreatic cancer are the Shizong Li and Xianglu Li have contributed equally to the work. * Xianglu Li [email protected] 1



Department of Hepatobiliary and Pancreatic Surgery, Hainan General Hospital, Haikou City 570311, Hainan Province, China



Department of Ward 1 of Oncology, Hainan General Hospital, No. 19, Xiuhua Road, Haikou City 570311, Hainan Province, China

2

distention of upper abdominal, pain, digestive tract diseases, thrombophlebitis, and anxiety [4]. When most patients with pancreatic cancer are diagnosed in the hospital, cancer cells have infiltrated the surrounding blood