MicroRNAs in adult high-grade gliomas: Mechanisms of chemotherapeutic resistance and their clinical relevance

Notorious for its high mortality rate, the current standard treatment for high-grade gliomas remains a challenge. This is largely due to the complex heterogeneity of the tumour coupled with dysregulated molecular mechanisms leading to the development of drug resistance. In recent years, microRNAs (miRNAs) have been considered to provide important information about the pathogenesis and prognostication of gliomas. miRNAs have been shown to play a specific role in promoting oncogenesis and regulating resistance to anti-glioma therapeutic agents through diverse cellular mechanisms. These include regulation of apoptosis, alterations in drug efflux pathways, enhanced activation of oncogenic signalling pathways, Epithelial-Mesenchymal Transition-like process (EMT-like) and a few others. With this knowledge, upregulation or inhibition of selected miRNAs can be used to directly affect drug resistance in glioma cells. Moreover, the clinical use of miRNAs in glioma management is becoming increasingly valuable. This comprehensive review delves into the role of miRNAs in drug resistance in high-grade gliomas and underscores their clinical significance. Our analysis has identified a distinct cluster of oncogenic miRNAs (miR-9, miR-21, miR-26a, miR-125b, and miR-221/222) and tumour suppressive miRNAs (miR-29, miR-23, miR-34a-5p, miR 181b-5p, miR-16-5p, and miR-20a) that consistently emerge as key players in regulating drug resistance across various studies. These miRNAs have demonstrated significant clinical relevance in the context of resistance to anti-glioma therapies. Additionally, the clinical significance of miRNA analysis is emphasised, including their potential to serve as clinical biomarkers for diagnosing, staging, evaluating prognosis, and assessing treatment response in gliomas.