miR-363-3p inhibits tumor growth by targeting PCNA in lung adenocarcinoma

// Yahong Wang 1, * , Ting Chen 1, * , Haili Huang 1 , Yun Jiang 1 , Lawei Yang 1 , Ziying Lin 1 , Huijuan He 1 , Tie Liu 4 , Bin Wu 2 , Jie Chen 3 , David W. Kamp 5 , Gang Liu 1, 2 1 Clinical Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China 2 Department of Respiratory Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China 3 Department of Cardiothoracic Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China 4 The First Affiliated Hospital, Medical School of Xi’an Jiaotong University, Xi’an, China 5 Department of Medicine, Northwestern University Feinberg School of Medicine and Jesse Brown VA Medical Center, Chicago, IL, USA * These authors have contributed equally to this work Correspondence to: Gang Liu, email: gangliu11@gdmc.edu.cn Keywords: miR-363-3p, lung adenocarcinoma, tumor growth, m-TOR/ERK signaling pathway, proliferating cell nuclear antigen (PCNA) Received: January 13, 2016     Accepted: January 10, 2017     Published: February 17, 2017 ABSTRACT Increasing evidence suggests that microRNAs play key roles in lung cancer. Our previous study demonstrated that microRNA 363-3p (miR-363-3p) is downregulated in lung cancer tissues. In this study, we demonstrated that overexpression of miR-363-3p inhibits the proliferation and colony formation of A549 and H441 cells, while silencing of miR-363-3p has the converse effects. The anti-oncogenic function of miR-363-3p was verified in a mouse tumor xenograft model. Furthermore, cell cycle analysis showed miR-363-3p can induce S phase arrest by downregulating Cyclin-D1 and upregulating Cyclin-dependent kinase-2 in lung adenocarcinoma cells. Additionally, miR-363-3p enhances cell apoptosis, whereas miR-363-3p inhibitor prevents apoptosis and leads to downregulation of Bax and Bak expression. The anti-proliferative function of miR-363-3p toward lung cancer cells may be explained by its ability to inhibit the activation of the mTOR and ERK signaling pathways. Using target prediction software and luciferase reporter assays, we identified PCNA as a specific target of miR-363-3p. miR-363-3p can decreased the accumulation of endogenous PCNA in lung adenocarcinoma cells. Moreover, exogenous expression of PCNA relieve the inhibition of miR-363-3p on cell proliferation, colony formation and mTOR and ERK signaling pathways. Taken together, our data indicate that miR-363-3p suppresses tumor growth by targeting PCNA in lung adenocarcinoma.