Down-regulation of lncRNA UCA1 enhances radiosensitivity in prostate cancer by suppressing EIF4G1 expression via sponging miR-331-3p

Cancer Cell Int. 2020 Sep 11:20:449. doi: 10.1186/s12935-020-01538-8. eCollection 2020.

Abstract

Background: We aimed to explore the role of long noncoding RNA urothelial carcinoma-associated 1 (lncRNA UCA1) and its underlying mechanism in the radioresistance of prostate cancer (PCa).

Methods: QRT-PCR was conducted to measure the expression of UCA1, microRNA-331-3p (miR-331-3p) and eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) in PCa tissues and cells. The relative protein level was determined by western blot assay. Cell proliferation and apoptosis were detected by MTT, colony formation assay, and flow cytometry, respectively. The target interaction between miR-331-3p and UCA1 or EIF4G1 was predicted through bioinformatics analysis, and verified by dual-luciferase reporter gene assay system.

Results: The high levels of UCA1 and EIF4G1 as well as the low level of miR-331-3p were observed in PCa tissues and cell lines. UCA1 and EIF4G1 expression were significantly upregulated by Gy radiation treatement. UCA1 or EIF4G1 knockdown repressed cell growth and enhanced cell apoptosis in 22RV1 and DU145 cells under radiation. Moreover, overexpression of EIF4G1 abolished UCA1 knockdown-induced effect on 6 Gy irradiated PCa cells. UCA1 sponged miR-331-3p to regulate EIF4G1 expression.

Conclusions: LncRNA UCA1 deletion suppressed the radioresistance to PCa by suppressing EIF4G1 expression via miR-331-3p. UCA1 acted as a potential regulator of radioresistance of PCa, providing a promising therapeutic target for PCa.

Keywords: EIF4G1; Prostate cancer; Radioresistance; UCA1; miR-331-3p.