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.
Highlights
Cervical cancer is one of the most common gynecological cancers in the worldwide [1, 2]
pyruvate kinase muscle isozyme M2 (PKM2) expression is associated with miR-let-7a, we explored and analyzed the expression of PKM2 in CC tissues and cell lines using
We demonstrated that the expression PKM2 mRNA was significantly elevated in the cancer tissues when compared with that in normal squamous epithelial tissues
Summary
Cervical cancer is one of the most common gynecological cancers in the worldwide [1, 2]. Emerging evidence has indicated that human papillomavirus plays an important role in the initiation and progression of cervical cancer. In this work, we endeavor to explore the signaling mechanisms that were involved in the development of cervical cancer. MiRNAs were reported to play an important role in some events involved in oncogenesis, such as cell survival, proliferation, apoptosis, migration and metastasis [8]. MiR-let-7a acts as a kind of new miRNAs, and has been featured by a tumor suppressor in different human tumors. MiR-let-7a targeted some related genes to affect signal pathways of tumors. As reported miR-let-7a has a close relationship with PKM2 signal pathway, and miR-let-7a exerts an anti-tumor effect on different tumors [9,10,11]. The role of miR-let-7a in proliferation and invasion of cervical cancer remains unknown
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