Long noncoding RNA UCA1 knockdown inhibits cisplatin-resistant cervical cancer tumorigenesis via the miR-195-5p/IKBKB axis.

Abstract

Cisplatin resistance is a major cause of poor prognosis in patients with cervical cancer. Dysregulation of long noncoding RNAs (lncRNAs) plays a key role in chemoresistance. Our results reveal that the lncRNA UCA1 is upregulated in cisplatin (DDP)-resistant cervical cancer tissues and HeLa cells. Mechanistically, the lncRNA UCA1 acts as a sponge for miR-195-5p, targeting IKBKB. UCA1 enhances proliferation, migration, and invasion while reducing apoptosis in DDP-resistant HeLa cells via the miR-195-5p/IKBKB axis. Additionally, UCA1 upregulates BNIP3Δex2 and p-p65 expressions and downregulates BNIP3 expression in DDP-resistant HeLa cells. Abnormal expressions of BNIP3Δex2 and BNIP3 significantly alter the malignant progression of HeLa/DPP cells. In vivo, UCA1 silencing inhibits growth, enhances apoptosis, and upregulates IKBKB, BNIP3Δex2, and p-p65 expressions while downregulating BNIP3 expression in subcutaneous xenografts in nude mice by targeting miR-195-5p. Overall, this study highlights a novel promising target for the treatment of DDP-resistant cervical cancer.