Oncotarget

Research Papers:

MiR-let-7a inhibits cell proliferation, migration, and invasion by down-regulating PKM2 in cervical cancer

Man Guo, Xinying Zhao, Xiaolei Yuan, Jing Jiang and Peiling Li _

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Oncotarget. 2017; 8:28226-28236. https://doi.org/10.18632/oncotarget.15999

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Abstract

Man Guo1, Xinying Zhao2, Xiaolei Yuan1, Jing Jiang1, Peiling Li1

1Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, P.R. China

2Department of Blood Dialysis, Heilongjiang Agricultural Reclamation Bureau General Hospital, Harbin, Heilongjiang, P.R. China

Correspondence to:

Peiling Li, email: leeplhmu@163.com

Keywords: miR-let-7a, PKM2, CC

Received: October 24, 2016     Accepted: February 28, 2017     Published: March 08, 2017

ABSTRACT

In recent decades, miRNA has been reported as a crucial modulator in some biology progressions. This work aims to assess the expression and role of miR-let-7a and pyruvate kinase muscle isozyme M2 (PKM2) in CC tissues and cell lines. Here, we identified that miR-let-7a expression was decreased in CC tissues, and SiHa and HeLa cells (all P < 0.001), however, PKM2 expression was increased in these samples. Statistically, miR-let-7a was inversely associated with PKM2 mRNA or protein (p = 0.013, p = 0.015, respectively). In-vitro assays revealed that ectopic miR-let-7a expression repressed SiHa and HeLa cell proliferation, migration and invasion, and enhanced SiHa and HeLa cell apoptosis. Furthermore, luciferase reporter assays revealed the 3'-UTR of PKM2 was identified a target of miR-let-7a, by which miR-let-7a affected the expression of PKM2 in SiHa and HeLa cells. Besides, PKM2 plasmids partially abrogated the inhibitory effects of miR-let-7a, while si-PKM2 enhanced the inhibitory effects of miR-let-7a. In vivo, miR-let-7a mimics indeed repressed tumor growth in mice xenograft model. In conclusion, our results demonstrated that miR-let-7a inhibits cell proliferation, migration and invasion by down-regulation of PKM2 in cervical cancer. miR-let-7a/PKM2 pathway may be a useful therapeutic target for CC patients.


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