Cancer Management and Research (Aug 2020)

Anti-Proliferative and Apoptosis-Promoting Effect of microRNA-125b on Pancreatic Cancer by Targeting NEDD9 via PI3K/AKT Signaling

  • Xue Y,
  • Zhong Y,
  • Wu T,
  • Sheng Y,
  • Dai Y,
  • Xu L,
  • Bao C

Journal volume & issue
Vol. Volume 12
pp. 7363 – 7373

Abstract

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Yuzheng Xue,1,* Yao Zhong,1,* Tielong Wu,1 Yingyue Sheng,1 Yuanyuan Dai,1 Lingling Xu,1 Chuanqing Bao2 1Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi 214041, Jiangsu, People’s Republic of China; 2Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi 214041, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuzheng XueDepartment of Gastroenterology, Affiliated Hospital of Jiangnan University, No. 585, Xingyuan North Road, Wuxi 214041, Jiangsu, People’s Republic of ChinaEmail [email protected]: The expression of microRNA-125b (miR-125b) is low in a variety of cancers, including gastric, lung, bladder, thyroid, and esophageal cancers. However, its specific mechanism in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study is aimed to explore the role of miR-125b in PDAC.Methods: PDAC tissues and adjacent tissues were collected for miR-125b analysis by qRT-PCR. Different PDAC cell lines were cultured for miR-125b detection by qRT-PCR, and CAPAN1 cells were selected for the downstream experiments. Cell proliferation was characterized by methyl thiazolyl tetrazolium (MTT) and 5-bromo-2-deoxyUridine (BrdU) staining. Flow cytometry was utilized for apoptosis and cell cycle changes. Cell invasion was determined by the Transwell assay and the dual-luciferase assay was utilized for validating the target gene. Western blotting was used to detect apoptosis related and PI3K/AKT signaling proteins.Results: miR-125b was significantly down-regulated in human PDAC tissues and cell lines (P < 0.05). miR-125b inhibited the growth and invasion of CAPAN1 cells, facilitated apoptosis, and blocked the cell cycle at the G0/G1 phase. Furthermore, miR-125 directly targeted NEDD9. The high expression of NEDD9 impaired the anti-proliferative and anti-apoptotic activity of miR-125b. miR-125b also inhibited apoptosis-related proteins and PI3K/AKT signaling pathways via NEDD9.Conclusion: miR-125b decreased cell growth and invasion, and facilitated apoptosis in CAPAN1 cells through PI3K/AKT inhibition via targeting NEDD9.Keywords: miR-125b, pancreatic ductal adenocarcinoma, apoptosis, NEDD9, PI3K/AKT

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