Abstract

BackgroundMicroRNAs play crucial roles in tumorigenesis and tumor progression. miR-770 has been reported to be downregulated in several cancers and affects cancer cell proliferation, apoptosis, metastasis and drug resistance. However, the role and underlying molecular mechanism of miR-770 in human glioma remain unknown and need to be further elucidated.MethodsThe expression of miR-770 in glioma tissues and cell lines was measured by quantitative real-time PCR (qRT-PCR) to explore the association of miR-770 expression with clinicopathological characteristics. The expression of CDK8 was detected by qRT-PCR and Western blotting in glioma tissues. A target prediction program and a dual-luciferase reporter assay were used to confirm that CDK8 is a target gene of miR-770. MTT and cell counting assays were used to assess the effect of miR-770 on glioma cell proliferation. The cell cycle distribution and apoptosis were examined by flow cytometry. CDK8 siRNA and overexpression were used to further confirm the function of the target gene.ResultsWe demonstrated that miR-770 expression was downregulated in human glioma tissues and cell lines. The overexpression of miR-770 inhibited glioma cell proliferation and cell cycle G1-S transition and induced apoptosis. The inhibition of miR-770 facilitated cell proliferation and G1-S transition and suppressed apoptosis. miR-770 expression was inversely correlated with CDK8 expression in glioma tissues. CDK8 was confirmed to be a direct target of miR-770 by using a luciferase reporter assay. The overexpression of miR-770 decreased CDK8 expression at both the mRNA and protein levels, and the suppression of miR-770 increased CDK8 expression. Importantly, CDK8 silencing recapitulated the cellular and molecular effects observed upon miR-770 overexpression, and CDK8 overexpression eliminated the effects of miR-770 overexpression on glioma cells. Moreover, both exogenous expression of miR-770 and silencing of CDK8 resulted in suppression of the Wnt/β-catenin signaling pathway.ConclusionsOur study demonstrates that miR-770 inhibits glioma cell proliferation and G1-S transition and induces apoptosis through suppression of the Wnt/β-catenin signaling pathway by targeting CDK8. These findings suggest that miR-770 plays a significant role in glioma progression and serves as a potential therapeutic target for glioma.

Highlights

  • MicroRNAs play crucial roles in tumorigenesis and tumor progression. miR-770 has been reported to be downregulated in several cancers and affects cancer cell proliferation, apoptosis, metastasis and drug resistance

  • These findings suggest that miR-770 plays a significant role in glioma progression and serves as a potential therapeutic target for glioma

  • Results miR‐770 is significantly downregulated in human glioma tissues and cell lines To analyze the expression status of miR-770 in human glioma tissues, we performed quantitative real-time PCR (qRT-PCR) to examine miR770 expression in clinical samples (63 glioma tissues and adjacent normal tissues) and glioma cell lines

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Summary

Introduction

MicroRNAs play crucial roles in tumorigenesis and tumor progression. miR-770 has been reported to be downregulated in several cancers and affects cancer cell proliferation, apoptosis, metastasis and drug resistance. The role and underlying molecular mechanism of miR-770 in human glioma remain unknown and need to be further elucidated. The incidence of glioma increased from 5.9 of 100, 000 people in 1973 to 6.61 of 100, 000 people in 2016, possibly as a consequence of improved radiological diagnosis [4]. Tremendous progress has been achieved in diagnosis and stratification of prognostication. Little progress has been achieved in treatment etc. The five-year overall survival of glioma patients in advanced stages remains poor [5]. It is critical to uncover the molecular mechanisms underlying glioma development and progression, and classification such as IDH status, ATRX/TERT, 1p/19q codeletion, histone gene mutations, which could reveal novel biomarkers and support the development of therapeutic strategies for patients with glioma

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