MIR-376-5P INHIBITS PROSTATE CANCER CELL PROLIFERATION AND INDUCES APOPTOSIS BY TARGETING TCTN1

Huan Cheng^#, Yue Chen^#, Song Xue, Rumin Wen, Jiacun Chen, Junqi Wang^* 

Department of Urology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou City, Jiangsu Province, China

Objective: miR-376-5p has been reported to be associated with a variety of tumors, including glioblastoma and breast cancer. However, its expression level and potential role in prostate cancer remain uncertain. The purpose of this study was to investigate the effects of miR-376-5p on the growth and migration of prostate cancer cells and the relevant molecular mechanisms.

Methods: Prostate cancer cell lines DU145 and 22RV1 were analyzed by CCK-8 assay and TUNEL staining to assess the effects of miR-376-5p over-expression on cell proliferation and apoptosis. The Transwell test was used to detect the migration capacity of DU145 and 22RV1 cells to evaluate the effect of miR-376-5p on cell migration. The targeting effect of miR-376-5p on TCTN1 was verified by western blot assay and double luciferase reporter assay.

Results: The expression of miR-376-5p was significantly down-regulated in clinical prostate cancer tissues and cells. Over-expression of miR-376-5p inhibited cell proliferation and induced apoptosis as assessed by CCK-8 assay and TUNEL staining. Transwell assay results showed that the over-expression of miR-376-5p inhibited cell migration. Through bioinformatics prediction and luciferase reporter gene detection, miR-376-5p was found to directly target tectonic family member 1 (TCTN1). Moreover, the over-expression of miR-376-5p significantly inhibited the expression of TCTN1. The expression of TCTN1 was significantly increased in prostate cancer and was inversely proportional to the content of miR-376-5p in prostate cancer tissues. We further found that TCTN1 over-expression reversed the effects of miR-376-5p transfection on the proliferation, migration, and apoptosis of prostate cancer cell lines.

Conclusion: miR-376-5p may play a tumor suppressor role in prostate cancer cells by negatively regulating the expression of TCTN1, suggesting that miR-376-5p and TCTN1 may be effective targets for prostate cancer treatment and intervention.