MicroRNA-342 inhibits the progression of glioma by directly targeting PAK4

Lu,Xianghe; Wang,Haowen; Su,Zhipeng; Cai,Lin; Li,Wenfeng

doi:10.3892/or.2017.5783

MicroRNA-342 inhibits the progression of glioma by directly targeting PAK4

Authors:
- Xianghe Lu
- Haowen Wang
- Zhipeng Su
- Lin Cai
- Wenfeng Li
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Affiliations: Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Radiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: July 3, 2017 https://doi.org/10.3892/or.2017.5783
Pages: 1240-1250

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Abstract

Glioma is an extremely aggressive and lethal type of brain tumour that originates from glial cells. MicroRNA (miRNA) dysregulation has been implicated in the occurrence and progression of many human cancers, including glioma. Thus, some specific miRNAs are potential therapeutic targets for glioma diagnosis, therapy and prognosis. MicroRNA-342 (miR‑342) has been reported to be abnormally expressed in various types of cancer. However, the precise roles of miR‑342 in glioma remain unknown. The present study showed that miR‑342 is relatively downregulated in glioma tissues and cell lines compared with that in adjacent normal tissues and normal human astrocytes. We observed that low miR‑342 expression levels are correlated with advanced WHO grades and low KPS scores of glioma patients. In addition, the results of the functional assays demonstrated that miR‑342 overexpression inhibits the proliferation and invasion of glioma cells and induces apoptosis. Further investigation revealed that P21 activated kinases 4 (PAK4) is a direct target of miR‑342 in glioma. PAK4 was significantly upregulated in glioma tissues and inversely correlated with miR‑342 expression. Moreover, PAK4 knockdown can mimic the effects of miR‑342 on glioma cell proliferation, invasion and apoptosis. Notably, restoration of expression of PAK4 reversed the suppressive effects induced by the miR‑342 in the glioma cells. The upregulation of miR‑342 inactivated the AKT and ERK pathways in glioma. These findings may contribute to the understanding of the molecular mechanism underlying the carcinogenesis and progression of glioma, and to provide novel therapeutic target for the treatment of glioma patients.

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