miR-139-5p activates ferroptosis by inhibiting the expression of HMG-CoA reductase to inhibit the progression of glioma.

in Cell death discovery by Zhongsheng You, Fei Wu, Yaofeng Zheng, Hongling Yang, Jianbo Ye, Hongyi Cai, Chuangcai Luo, Yang Liu, Yiquan Ke, Xiangdong Xu

TLDR

  • The study found that miR-139-5p overexpression promotes ferroptosis and inhibits glioma progression by downregulating HMGCR expression, and showed a synergistic effect with simvastatin.
  • The results suggest miR-139-5p as a potential therapeutic target for glioma treatment, particularly in combination with simvastatin.

Abstract

Glioma is the most aggressive and common tumour in the central nervous system. It has been reported that miR-139-5p plays an important role in regulating tumour progression. However, whether miR-139-5p affects the progression of glioma and the specific mechanism remains to be explored. Through experiments involving down-regulation or overexpression of miR-139-5p and treatment with simvastatin (SIM), qRT-PCR and Western Blot were used to detect the expression levels of related genes. Transmission electron microscopy (TEM) and corresponding kits were used to detect the changes in ferroptosis and cholesterol content in glioma cells. RNA-seq analysis was used to explore the specific mechanism by which miR-139-5p regulates ferroptosis. Our results demonstrate that miR-139-5p expression is significantly reduced in glioma cells compared to normal glial cells and is associated with poor prognosis. Overexpression of miR-139-5p promotes ferroptosis and inhibits tumour cell proliferation by downregulating HMG-CoA reductase (HMGCR) expression, consequently hindering glioma progression. Additionally, we found a synergistic effect between miR-139-5p overexpression and SIM treatment in promoting ferroptosis in gliomas. These findings suggest that miR-139-5p could serve as a potential therapeutic target for glioma treatment, particularly in combination with SIM. This study demonstrated that miR-139-5p promoted ferroptosis in glioma cells by down-regulating HMGCR expression and cholesterol synthesis. Moreover, miR-139-5p and SIM had a synergistic effect in promoting ferroptosis to prevent glioma progression.

Overview

  • The study investigated the role of miR-139-5p in regulating glioma progression and explored its specific mechanism.
  • The researchers used a combination of experimental approaches, including miR-139-5p overexpression and down-regulation, treatment with simvastatin, and RNA-seq analysis.
  • The primary objective of the study was to identify miR-139-5p as a potential therapeutic target for glioma treatment, particularly in combination with simvastatin.

Comparative Analysis & Findings

  • The results showed that miR-139-5p expression was significantly reduced in glioma cells compared to normal glial cells and was associated with poor prognosis.
  • Overexpression of miR-139-5p promoted ferroptosis and inhibited tumour cell proliferation by downregulating HMG-CoA reductase (HMGCR) expression.
  • A synergistic effect was found between miR-139-5p overexpression and simvastatin treatment in promoting ferroptosis in gliomas.

Implications and Future Directions

  • The findings suggest that miR-139-5p could serve as a potential therapeutic target for glioma treatment, particularly in combination with simvastatin.
  • Further studies are needed to investigate the molecular mechanisms underlying the synergistic effect of miR-139-5p and simvastatin.
  • Future research could also explore the potential clinical application of miR-139-5p-based therapies in combination with other anti-cancer agents.
Read Full Article