SPACA6-hosted miR-99b~125a~let-7e cluster shapes melanoma resistance by modulating mTOR-mediated immunosuppression.

ABSTRACT: Genomic, non-genomic, and immune alterations contribute to melanoma resistance to BRAF and MEK inhibitors. Here, we investigated the role of the SPACA6-hosted miR-99b~125a~let-7e cluster in modulating inflammatory processes and therapy resistance. We found that miR-99b, miR-125a, and let-7e were upregulated in progressing tumors from treated melanoma patients compared with untreated lesions, and in patients with short response duration compared with long-term responders. Similarly, miR-99b~125a~let-7e expression levels were high in melanoma cell lines with acquired resistance to BRAF/MEK inhibitors, showing upregulation of immunosuppressive cytokines. Combined inhibition of miR-99b, miR-125a and let-7e during drug treatment reduced proliferation of resistant cells and decreased the express

SUBMITTER: Vallacchi V 

PROVIDER: S-EPMC12808473 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature