Long non-coding RNA CASC2 enhances cisplatin sensitivity in oral squamous cell cancer cells by the miR-31-5p/KANK1 axis.

Abstract

Oral squamous cell cancer (OSCC) is a primary malignant tumor of the head and neck. Long non-coding RNA cancer susceptibility candidate 2 (CASC2) is related to the chemoresistance of diverse tumors. At present, the resistance of OSCC to first-line chemotherapy drug cisplatin (DDP) is still a giant problem. Herein, we investigated the role and mechanism of CASC2 in OSCC resistance to DDP. Expression levels of CASC2, miR-31-5p, and KANK1 in OSCC tissues and cells were determined by qRT-PCR. The half-maximal inhibitory concentration (IC50) value of DDP-resistant OSCC cells and apoptosis of DDP-resistant OSCC cells were determined via CCK-8 or flow cytometry assays. The relationship between CASC2 or KANK1 and miR-31-5p was verified with a dual-luciferase reporter or RIP assays. The role of CASC2 in vivo was confirmed by xenograft experiments. We observed that CASC2A and KANK1 were downregulated while miR-31-5p was upregulated in DDP-resistant OSCC tissues and cells (p<0.05). CASC2 overexpression enhanced cell DDP sensitivity and accelerated cell apoptosis in DDP-resistant OSCC cells in vivo and in vitro (p<0.05). Notably, KANK1 acted as a target for miR-31-5p. Also, CASC2 modulated KANK1 expression via sponging miR-31-5p in DDP-resistant OSCC cells (p<0.05). Both CASC2 and KANK1 introduction-mediated impacts on the DDP sensitivity and apoptosis of DDP-resistant OSCC cells were restored by miR-31-5p elevation (p<0.05). To conclude, CASC2 boosted the DDP sensitivity and apoptosis of DDP-resistant OSCC cells by upregulating KANK1 via sponging miR-31-5p, and CASC2 might be a potential target for DDP-resistant OSCC treatment.