Long non-coding RNA CASC2 regulates Sprouty2 via functioning as a competing endogenous RNA for miR-183 to modulate the sensitivity of prostate cancer cells to docetaxel

Prostate cancer (PC) is the most common cancer in men; however, limited effect is obtained due to the therapy resistance. CASC2 acts as a tumor suppressor in human malignancies serving as a ceRNA for miRNAs; Sprouty2 (SPRY2), a key antagonist of RTK signalling, also serves as a tumor suppressor. Herein, CASC2 and SPRY2 expression was down-regulated in PC tissues and cell lines; the overexpression of CASC2 and SPRY2 could suppress PC cell proliferation, promote PC cell apoptosis, and enhance the sensitivity of PC cells to docetaxel. CASC2 positively regulated SPRY2 expression and inhibited downstream extracellular regulated protein kinases (ERK) signaling activation through SPRY2. By using online tools, miR-183 might be a direct target of CASC2, and might simultaneously bind to the 3'UTR of SPRY2. The direct binding between CASC2, miR-183 and SPRY2 was then validated; miR-183 inhibition enhanced the cytotoxicity of docetaxel on PC cells, which could be partially attenuated by SPRY2 knockdown. In summary, CASC2 competes with SPRY2 for miR-183 binding to rescue the expression of SPRY2 in PC cells, thus enhancing the sensitivity of PC cells to docetaxel through SPRY2 downstream ERK signaling pathway; CASC2 and SPRY2 might be novel adjuvants for docetaxel-based chemotherapy for PC.

Archives of biochemistry and biophysics. 2018 Jan 23 [Epub ahead of print]

Weiyin Gao, Shuangquan Lin, Cheng Cheng, Anyi Zhu, Yingbo Hu, Zimin Shi, Xiao Zhang, Zhengdong Hong

Department of Urology Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, PR China., Department of Urology Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, PR China. Electronic address: .