The role of miRNA-10b and miRNA-21 in radioresistance and temozolomide resistance of high-grade glioma patients: a systematic review

OBJECTIVE Despite optimal therapy, high-grade glioma (HGG) still has a very unfavorable prognosis. Gross-total resection is not often possible, and even when it is, many patients still succumb to the disease due to resistance to temozolomide (TMZ) and radiotherapy. As the mechanism behind such resistance is multifactorial, microribonucleic acids (miRNAs) with their wide-ranging epigenetic effects on cancer have emerged as potential research targets. Among others, miRNA-10b and miRNA-21 are the most widely studied miRNAs in HGG. In this review, the authors aimed to investigate the role and predictive value of miRNA-10b and miRNA-21 in TMZ and radiotherapy resistance in HGG patients. METHODS The PubMed, Europe PMC, and Web of Science databases were searched to find in vitro, in vivo, or clinical studies assessing the relationship between miRNA-10b and miRNA-21 expression with TMZ resistance, radiotherapy resistance, and survival. Review articles, editorials, correspondence, case reports, case series, non–English-language articles, and studies that only analyzed datasets were excluded. Results were then synthesized according to those three outcomes. This review has been registered in PROSPERO (International Prospective Register of Systematic Reviews) under registration no. CRD1004470. RESULTS There were 34 studies included in this review, with 25 studies evaluating miRNA-21, 6 studies evaluating miRNA-10b, and 3 studies evaluating both miRNA-10b and miRNA-21. The results of the in vitro and in vivo studies were unequivocal in demonstrating that miRNA-10b and miRNA-21 expression correlated with resistance. The two miRNAs increased tumor stemness, viability, invasiveness, and resistance to apoptosis. However, not all the clinical studies demonstrated a significant relationship between both miRNAs and survival. This was possibly caused by differences in resection status and sampling method. CONCLUSIONS MiRNA-10b and miRNA-21 expression correlated with TMZ and radiotherapy resistance in vivo and in vitro. With properly designed human studies, these results could translate to tremendous benefits in the clinical field. Future clinical studies should be designed to better account for resection status and sampling method.