MiR-3619-5p hampers proliferation and cisplatin resistance in cutaneous squamous-cell carcinoma via KPNA4.

ABSTRACT

Cutaneous squamous cell carcinoma (CSCC) remains the second most prevailing cancer worldwide and presents high mortality rates. Given that chemoresistance becomes an enormous obstacle to the therapy for CSCC patients, there is a pressing need to discover novel strategies for enhancing the response of CSCC cells to cisplatin. Emerging evidence has unfolded that miRNAs are participated in regulation of drug resistance in multiple cancers. MiR-3619-5p has been proofed to exert tumor inhibitive activities in human malignancies, but the biological function of miR-3619-5p in the progression of CSCC is still unclear. In this study, we observed that miR-3619-5p expression was pronouncedly dropped in cisplatin-resistant CSCC cells. Subsequently, miR-3619-5p was validated to act as a tumor suppressor in CSCC through retarding cell proliferation and cisplatin resistance. Besides, our findings certified that KPNA4 was highly expressed in cisplatin-resistant CSCC cells. Further, KPNA4 was negatively regulated by miR-3619-5p. Rescue experiments unveiled that KPNA4 counteracted the miR-3619-5p-mediated regulation of CSCC tumorigenesis. On the whole, miR-3619-5p inhibited cell proliferation and cisplatin resistance of CSCC by regulating KPNA4 expression, suggesting that miR-3619-5p/KPNA4 pathway may represent a potential promising strategy for the treatment of patients with CSCC.