Methylation associated miR-1246 contributes to poor prognosis in gliomas treated with temozolomide

Glioblastoma (GBM) is the most aggressive type of glioma. In this study, we aimed to investigate the biological functions and the possible mechanisms of miR-1246 in glioma.

A miRNA-seq array was conducted in both the tumor tissues and the glioma cell lines treated with 5-Aza to determine the methylation statues of miRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to verify the miR-1246 expressions. We used overall survival (OS) and the progress-free survival (PFS) to investigate the clinical significance of miR-1246 in the prognosis of glioma patients. Additionally, bioinformatic analysis was used for discovering the potential targets of miR-1246. Cell viability, wound-healing assay and protein expression tests were conducted after the transfection or knockdown of miR-1246 and CCNG2, respectively.

We found the reduced expression of miR-1246 in IDH1^MUT tumor tissues and the increased expression in the glioma cell lines treated with 5-Aza. Therefore, miR-1246 was selected as a candidate for further analysis. Kaplan-Meier analysis showed that the glioma patients with the high level of miR-1246 had the worst survival rate compared to the low level counterparts. Overexpression of miR-1246 promoted cell proliferation, migration and invasion in glioma cells. Moreover, the results showed that the downregulation of miR-1246 decreased chemoresistance by targeting CCNG2. In addition, Gene ontology (GO) analysis revealed that miR-1246 was associated with the regulations of transcription, cell cycle, cell proliferation, cell adhesion and apoptosis.

These results indicated that the miR-1246/CCNG2 axis might be a potential target for improving the drug resistance in glioma.