Oncotarget

Research Papers:

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

Yahong Wang, Ting Chen, Haili Huang, Yun Jiang, Lawei Yang, Ziying Lin, Huijuan He, Tie Liu, Bin Wu, Jie Chen, David W. Kamp and Gang Liu _

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Oncotarget. 2017; 8:20133-20144. https://doi.org/10.18632/oncotarget.15448

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Abstract

Yahong Wang1,*, Ting Chen1,*, Haili Huang1, Yun Jiang1, Lawei Yang1, Ziying Lin1, Huijuan He1, Tie Liu4, Bin Wu2, Jie Chen3, David W. Kamp5, Gang Liu1,2

1Clinical Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China

2Department of Respiratory Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China

3Department of Cardiothoracic Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China

4The First Affiliated Hospital, Medical School of Xi’an Jiaotong University, Xi’an, China

5Department 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: [email protected]

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.


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