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

ESDR441 - MiR-23b functions as a tumor suppressor in cutaneous squamous cell carcinoma and targets Ras-related 2 (RRAS2)

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.