LncRNA UCA1 promotes proliferation and cisplatin resistance of oral squamous cell carcinoma by sunppressing miR-184 expression.

Abstract

Chemotherapy resistance has become the main obstacle for the effective treatment of human cancers. Long non‐coding RNA urothelial cancer associated 1 (UCA1) is generally regarded as an oncogene in some cancers. However, the function and molecular mechanism of UCA1 implicated in cisplatin (CDDP) chemoresistance of oral squamous cell carcinoma (OSCC) is still not fully established. UCA1 expression in tumor tissues and cells was tested by qRT‐PCR. MTT, flow cytometry and caspase‐3 activity analysis were explored to evaluate the CDDP sensitivity in OSCC cells. Western blot analysis was used to measure BCL2, Bax and SF1 protein expression. Luciferase reporter assay was conducted to investigate the molecular relationship between UCA1, miR‐184, and SF1. Nude mice model was used to confirm the functional role of UCA1 in CDDP resistance in vivo. UCA1 expression was upregulated in OSCC tissues, cell lines, and CDDP resistant OSCC cells. Function analysis revealed that UCA1 facilitated proliferation, enhanced CDDP chemoresistance, and suppressed apoptosis in OSCC cells. Mechanisms investigation indicated that UCA1 could interact with miR‐184 to repress its expression. Rescue experiments suggested that downregulation of miR‐184 partly reversed the tumor suppression effect and CDDP chemosensitivity of UCA1 knockdown in CDDP‐resistant OSCC cells. Moreover, UCA1 could perform as a miR‐184 sponge to modulate SF1 expression. The OSCC nude mice model experiments demonstrated that depletion of UCA1 further boosted CDDP‐mediated repression effect on tumor growth. UCA1 accelerated proliferation, increased CDDP chemoresistance and restrained apoptosis partly through modulating SF1 via sponging miR‐184 in OSCC cells, suggesting that targeting UCA1 may be a potential therapeutic strategy for OSCC patients