Let-7a-3p Associated with Glioblastoma Progression and Recurrence after Bevacizumab Treatment

The let-7 family, along with its regulatory targets, plays a crucial role in various cellular functions, including cell proliferation, differentiation, and the maintenance of pluripotency. Dysregulation of let-7 family members is frequently observed in many types of cancer, including glioblastoma (GBM). In our previous research, we classified GBM into bevacizumab (BVZ)-responsive and non-responsive subtypes using machine learning algorithms, identifying miR-21, miR-10b, and miR-197 as biomarkers. In this study, we focused on let-7a-3p and its role in the E2F8 regulatory networks following BVZ treatment in the responsive subtype of GBM. We investigated the potential decrease in expression levels of let-7a-3p in BVZ-responsive GBM subtypes after treatment and analyzed its associated regulatory network. Notably, we discovered that several targets of let-7a-3p, including MRPL35, GSK3B, and FAM107B, were upregulated following BVZ treatment in the responsive subtype. Our bioinformatics analyses suggest that these significant increases in target expression after BVZ treatment may promote angiogenesis, stem cell proliferation, tumorigenesis, and chemoresistance, which could contribute to GBM recurrence and progression post-treatment.