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, Gang Liu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)20133-20144
Number of pages12
JournalOncotarget
Volume8
Issue number12
DOIs
StatePublished - 2017

Keywords

  • Lung adenocarcinoma
  • M-TOR/ERK signaling pathway
  • Proliferating cell nuclear antigen (PCNA)
  • Tumor growth
  • miR-363-3p

ASJC Scopus subject areas

  • Oncology

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