441 MiR-23b functions as a tumor suppressor in cutaneous squamous cell carcinoma and targets Ras-related 2 (RRAS2)

Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancer types with metastatic potential. MicroRNAs (miRNAs) are small RNAs that regulate gene expression at posttranscriptional level. Here, we report miR-23b, an evolutionarily conserved miRNA abundantly expressed in keratinocytes, downregulated cSCCs and to a lesser extent precancerous lesions. We show miR-23b regulated by MAPK-signaling pathway. CRISPR/Cas9-mediated deletion MIR23B cSCC lines resulted increased colony formation tumor sphere ability. Conversely, ectopic overexpression suppressed capacity cells form colonies spheroids. Moreover, decreased ability induce angiogenesis vitro. In line these results, transcriptomic analysis revealed led suppression transcripts belonging key oncogenic pathways including cells. vivo, significantly reduced growth. Mechanistically, identified Ras-related protein RRAS2 as direct target found overexpressed human there negative correlation between RRAS2-expression supporting importance miR-23b: RRAS2-interaction. Altogether, our results suggest acts suppressor its loss contributes progression.