OncoTargets and Therapy (Oct 2019)
MicroRNA-503 Inhibits Non-Small Cell Lung Cancer Progression By Targeting PDK1/PI3K/AKT Pathway
Abstract
Yingying Wei,1 Yuanfan Liao,2 Yu Deng,2 Yukun Zu,2 Bo Zhao,2 Fan Li2 1Department of Pharmacy, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; 2Department of Thoracic Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of ChinaCorrespondence: Fan LiDepartment of Thoracic surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jie Fang Avenue, Hankou, Wuhan 430030, People’s Republic of ChinaEmail [email protected]: The aim of the study was to study the role of dysregulated expression of a microRNA (miRNA), miR-503, in non-small-cell lung cancer (NSCLC) and investigate the underlying mechanism.Methods: Quantitative real-time PCR (qRT-PCR) and in situ hybridization staining (ISH) were used to evaluate the expression level of miR-503 in NSCLC tissues and paired adjacent tissues. CCK-8, colony formation and flow cytometry were performed to explore the effects of miR-503 overexpression on cell proliferation, colony formation and apoptosis. Cells with miR-503 overexpression were used to initiate xenograft models. Dual luciferase reporter assay, qRT-PCR, immunohistochemistry and Western blotting were conducted to investigate the interaction of miR-503 and its potential target.Results: Significantly downregulated miR-503 was found in NSCLC tumor tissues and cell lines. miR-503 overexpression significantly inhibited NSCLC cell proliferation, migration and invasion. PDK1 was predicted as the direct targets of miR-503. PDK1 overexpression reversed the inhibitory effects of miR-503 on biological functions, while PDK1 silencing significantly counteracted miR-503 inhibitor-induced pro-tumor effects in A549 cells. Mechanistically, upregulation of miR-503 inhibited PDK1 expression and subsequently caused the inactivation of PI3K/AKT pathway.Conclusion: Our results suggest that miR-503 inhibits NSCLC progression by targeting PDK1/PI3K/AKT pathway, potentiating the use of miR-503 as a biomarker and therapeutic target for NSCLC.Keywords: miR-503, non-small cell lung cancer, PDK1, proliferation, mortality
