Tumor progression is effectively suppressed by miR-195 through direct targeting of YAP1.

BACKGROUND: Yes-associated protein 1 (YAP1) dysregulation is frequently observed in various human cancers. This study aimed to identify microRNAs (miRNAs) capable of suppressing YAP1 expression and to elucidate their functional roles in tumor progression. METHODS: We screened five candidate miRNAs using a luciferase reporter assay containing the YAP1 3' untranslated region (3' UTR). Functional validation was performed using gain- and loss-of-function experiments in HCT116 and A549 cell lines. The in vivo effects of miR-195 were evaluated using a xenograft model. RESULTS: Among the tested miRNAs, miR-195 demonstrated the most potent suppression of YAP1 3' UTR activity. This interaction was direct and specific, as a mutation in the YAP1 3' UTR seed sequence abolished miR-195-mediated repression. Consequently, miR-195 overexpression significantly reduced endogenous YAP1 protein levels and suppressed the expression of its downstream target, CTGF. Functionally, miR-195 overexpression inhibited cell viability and reduced colony formation by approximately 40% in HCT116 cells, while miR-195 knockdown promoted proliferation. Rescue experiments confirmed that the anti-proliferative effects of miR-195 were dependent on YAP1 suppression. In vivo, stable overexpression of miR-195 significantly attenuated tumor growth in xenograft models. Furthermore, analysis of clinical data revealed that downregulation of miR-195 is prevalent in multiple tumor types and correlates with poor patient survival. CONCLUSION: Our findings establish miR-195 as a critical tumor suppressor that directly targets YAP1, highlighting its potential as a therapeutic target in cancer treatment.