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

AI Article Synopsis

  • The study focused on the role of miR-1246 in glioblastoma (GBM), a highly aggressive brain tumor, exploring its biological functions and mechanisms.
  • Researchers found that miR-1246 expression was lower in tumor tissues but increased in treated glioma cell lines, suggesting a complex relationship with tumor progression.
  • High levels of miR-1246 were linked to poor survival rates in patients, with evidence showing it enhances cell proliferation and invasion while targeting CCNG2 to influence chemoresistance.

Article Abstract

Objective: 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.

Methods: 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.

Results: We found the reduced expression of miR-1246 in IDH1 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.

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

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Source
http://dx.doi.org/10.1016/j.clineuro.2020.106344DOI Listing

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