The Study On MiR-92b Inhibit Gliomas Malignant Phenotype In Vitro

Background and objective:Glioma is the most common primary tumor of the central nervous system. Owing to the invasive growth and rapid cell proliferation, the malignant glioma is hardly to be cured by the currently available therapeutic approaches, such as surgical resection, postoperative radiotherapy, chemotherapy and immunotherapy etc. It has high recurrence rate and the prognosis is poor. This situation partially dues to our poor understanding of the etiology and pathogenesis of gliomas. Therefore, a more comprehensive understanding of the molecular pathology of gliomas must be sought for searching new targets treatment glioma and optimizing treatment strategies and development of novel therapeutic approaches.Several studies had showed that Nemo-like kianse(NLK) is a cancer suppressor gene, the study of cancer cell lines in vitro revealed that it suppress cancer through promote cancer cell apoptosis such as colon cancer DLD-1cell lines, breast cancer cell lines and glioma cell line. However, the study of NLK in glioma is rare, these evidences indicated that NLK could be a new tumor suppressor gene. In order to find the microRNAs in gliomas that could regulate NLK. We searched several microRNA target prediction database, such as TARGETSCAN and MIRANDA and several different miRNAs were predicted to have NLK as putative target, including miR-92b. So the present study is to focus on regulation of malignant phenotype in gliomas by miR-92b I. Methods and results:The present study was divided into two partsIn the first part of this study, miR-92b expression was examined in5malignant glioma cell lines and38freshly resected glioma samples by Real time PCR. It was found that these microRNAs were upregulated in gliomas, and their expression was positively correlated with the tumor grade.In the second part, we transfected miR-92b I to the human glioma cell lines SNB19and LN229. Real time PCR was conducted to detect the expression of miR-92b in transfected cells. The cell proliferation rate was determined by3-(4,5-Dime--thylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell cycle kinetics was detected by flowcytometry. The cell apoptosis was examined by Annexin V assay and invasive ability was evaluated by transwell assay. The results showed that the expression of miR-92b in the cells transfected with miR-92b I was significantly downregulated. The cell proliferation activity and invasive ability were reduced, cells were arrested in G0/G1phase, and apoptosis was induced in cell groups transfected with miR-92b I as compared to those of the cells transfected with control cells. These findings showed that miR-92b is a OncomiRs which can promote the growth of glioma.Conclusion:The results demonstrate that miR-92b expression are significantly increased in the majority of the gliomas and its expression is positively correlated with the tumor grade. Transfection of miR-92b I into the glioma cells is able to inhibit the glioma cell proliferation activity, invasive ability, arrest the cells in G0/G1pahse, and induce cell apoptosis. Thus, miR-92b is identified as oncomiRs which implicate that they can be candidate targets for gene therapy of gliomas. To our knowledge, this is the first comprehensive study on the expression and the potential mechanism of miR-92b in gliomagenesis. These evidences provide us the molecular pathologic machnism and a new class of targeted therapeutic strategy for human gliomas.