Genome-Wide CRISPR Screen Identifies a microRNA Orchestrating Pleiotropic Resistance to Targeted Therapy and T Cell Immunity in Melanoma - PubMed
3 hours ago
- #miR-18a
- #melanoma resistance
- #CRISPR screen
- A genome-wide CRISPR screen identifies miR-18a as a key regulator of pleiotropic resistance in melanoma, contributing to both targeted therapy resistance and impaired T cell immunity.
- miR-18a deficiency drives resistance via two mechanisms: derepressing AJUBA-regulated Hippo signaling during MAPK inhibition and enhancing THBS1-CD47 interactions, which disrupt the immunological synapse with CD8+ T cells.
- The protein hnRNP A1 modulates miR-18a expression, playing an essential role in mediating cross-resistance between targeted therapies and immunotherapies.
- Targeting non-coding RNA vulnerabilities, such as miR-18a, may offer a therapeutic strategy to overcome complex resistance and improve outcomes in melanoma treatment.