miR-218 inhibits the proliferation of glioma U87 cells through the inactivation of the CDK6/cyclin D1/p21Cip1/Waf1 pathway

Jun,Gu  Jian; Zhong,Gao  Guang; Ming,Zhang  Shi

doi:10.3892/ol.2015.3068

miR-218 inhibits the proliferation of glioma U87 cells through the inactivation of the CDK6/cyclin D1/p21Cip1/Waf1 pathway

Authors:
- Gu Jian Jun
- Gao Guang Zhong
- Zhang Shi Ming
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Affiliations: Department of Neurosurgery, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China, Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
Published online on: March 23, 2015 https://doi.org/10.3892/ol.2015.3068
Pages: 2743-2749

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Abstract

Malignant gliomas are the most common and deadly primary brain tumors in adults and the high proliferative ability of these cells is one of the most important causes of the poor prognosis of this cancer. Suppressing the proliferation of malignant gliomas cells by altering effector molecules can significantly improve the prognosis of a patient. microRNAs (miRNAs) are small non‑coding RNA molecules ~22 nucleotides in length that are able to function as oncogenes or tumor suppressors in human cancer. In the present study, it was demonstrated that the expression level of miRNA‑218 (miR‑218) is markedly downregulated in glioma cell lines and human primary glioma tissues. Upregulation of miR‑218 in glioma U87 cells dramatically inhibited the proliferation by inducing G1‑S checkpoint arrest. Furthermore, it was demonstrated that ectopically expressing miR‑218 in glioma U87 cells results in the downregulation of the expression of cyclin dependent kinase (CDK)6 and cyclin D1 and upregulation of the expression of p21Cip1/Waf1. In addition, it was identified that miR‑218 inactivated the CDK6/cyclin D1/p21Cip1/Waf1 pathway by downregulating CDK6 expression through the direct targeting of the 3'‑untranslated region of CDK6. The present results suggest that miR‑218 plays an important role in the prevention of the proliferation of glioma cells, and the present study also revealed a novel mechanism for miRNA‑mediated direct suppression of the CDK6/cyclin D1/p21Cip1/Waf1 pathway in glioma cells.

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