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Oncotarget. 2017 Apr 25;8(17):28226-28236. doi: 10.18632/oncotarget.15999.

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

Author information

1
Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, P.R. China.
2
Department of Blood Dialysis, Heilongjiang Agricultural Reclamation Bureau General Hospital, Harbin, Heilongjiang, P.R. China.

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.

KEYWORDS:

CC; PKM2; miR-let-7a

PMID:
28415668
PMCID:
PMC5438645
DOI:
10.18632/oncotarget.15999
[Indexed for MEDLINE]
Free PMC Article

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