Circular RNA cir‐ITCH Is a Potential Therapeutic Target for the Treatment of Castration‐Resistant Prostate Cancer
Shoubin Li, Chunhong Yu, Yunxia Zhang, Junjiang Liu, Yi Jia, Fuzhen Sun, Panying Zhang, Jingpo Li, Liuxiong Guo, Helong Xiao, Fei Gao, Xinna Deng, Ziqi Cai, Jianhui Cai
Abstract
cir‐ITCH, a well‐known tumor‐suppressive circular RNA, plays a critical role in different cancers. However, its expression and functional role in prostate cancer (PCa) are unclear. Herein, we explored the potential mechanism and tumor‐inhibiting role of cir‐ITCH in PCa. Using reverse transcriptase polymerase chain reaction assay, we analyzed the expression of cir‐ITCH in PCa and paired adjacent nontumor tissue samples resected during surgical operation, as well as in two cell lines of human PCa (LNCaP and PC‐3) and the immortalized normal prostate epithelial cell line (RWPE‐1). Cell viability and migration of PCa cell lines were evaluated using CCK‐8 and wound‐healing assays. Expression of key proteins of the Wnt/ β ‐catenin and PI3K/AKT/mTOR pathways was detected using western blotting. We found that cir‐ITCH expression was typically downregulated in the tissues and cell lines of PCa compared to that in the peritumoral tissue and in RWPE‐1 cells, respectively. The results showed that cir‐ITCH overexpression significantly inhibits the proliferation, migration, and invasion of human PCa cells and that reciprocal inhibition of expression occurred between cir‐ITCH and miR‐17. Proteins in the Wnt/ β ‐catenin and PI3K/AKT/mTOR pathways were downregulated by overexpression of cir‐ITCH both in androgen receptor‐positive LNCaP cells and androgen receptor‐negative PC‐3 cells. Taken together, these data demonstrated that cir‐ITCH plays a tumor‐suppressive role in human PCa cells, partly through the Wnt/ β ‐catenin and PI3K/AKT/mTOR pathways. Thus, cir‐ITCH may serve as a novel therapeutic target for the treatment of PCa, especially castration‐resistant prostate cancer.