Fang Xiao1, Yueran Li1, Yajun Wan2, Min Xue3. 1. Department of Gynecology and Obstetrics, The Third Xiangya Hospital of Central South University, No. 138, Tong zi po Rd, Yuelu District, Changsha, 410013, China. 2. Department of Gynecology and Obstetrics, The Third Xiangya Hospital of Central South University, No. 138, Tong zi po Rd, Yuelu District, Changsha, 410013, China. 493289071@qq.com. 3. Department of Gynecology and Obstetrics, The Third Xiangya Hospital of Central South University, No. 138, Tong zi po Rd, Yuelu District, Changsha, 410013, China. 215277245@qq.com.
Abstract
PURPOSE: Ovarian cancer remains a most malignant female cancer nowadays. The acquisition of chemoresistance to common-used cisplatin-based chemotherapy results in a decreased overall patient survival. The present study is aimed to investigate the role and mechanism by which miR-139/ ATPases7A/B axis modulates the chemoresistance of ovarian cancer to cisplatin-based chemotherapy. METHODS: The expression of miR-139 in cisplatin-sensitive (n = 23) and cisplatin-resistant (n = 14) ovarian cancer tissues and cell lines (CAOV-3 and SNU119) was determined using real-time PCR assays; its effect on ovarian cancer cell chemoresistance to different concentrations of cisplatin was then assessed by measuring the cell viability using MTT assays. Next, miR-139 binding to the 3'UTR of ATP7A/B was confirmed using luciferase reporter gene assays. Finally, the combined effect of miR-139 and ATP7A/B on the chemoresistance of ovarian cancer cell was assessed. RESULTS: miR-139 expression was down-regulated in cisplatin-resistant ovarian cancer tissues (**P < 0.01) and reduced by cisplatin treatment in ovarian cell lines (*P < 0.05, **P < 0.01); miR-139 could enhance cisplatin-induced suppression on ovarian cancer cell viability, shown as reduced lC50 values; ATP7A and ATP7B protein levesincreased approximately 2 ~ fold-changein cisplatin-resistant cell lines. MiR-139 directly bound to the 3'UTR of ATP7A/B, respectively; miR-139 inhibition increased lC50 values whereas ATP7A/B knockdown reduced lC50 values of CAOV-3 and SNU119 cell lines under cisplatin treatment; the effect of miR-139 inhibition could be partially attenuated by ATP7A/B knockdown. CONCLUSIONS: MiR-139/ATP7A/B axis can be a reliable biomarker for ovarian cancer diagnosis, and may affect the chemoresistance of ovarian cancer to cisplatin-based chemotherapy; rescuing miR-139 expression thus to inhibit ATP7A/B might contribute to dealing with the chemoresistance of ovarian cancer.
PURPOSE:Ovarian cancer remains a most malignant female cancer nowadays. The acquisition of chemoresistance to common-used cisplatin-based chemotherapy results in a decreased overall patient survival. The present study is aimed to investigate the role and mechanism by which miR-139/ ATPases7A/B axis modulates the chemoresistance of ovarian cancer to cisplatin-based chemotherapy. METHODS: The expression of miR-139 in cisplatin-sensitive (n = 23) and cisplatin-resistant (n = 14) ovarian cancer tissues and cell lines (CAOV-3 and SNU119) was determined using real-time PCR assays; its effect on ovarian cancer cell chemoresistance to different concentrations of cisplatin was then assessed by measuring the cell viability using MTT assays. Next, miR-139 binding to the 3'UTR of ATP7A/B was confirmed using luciferase reporter gene assays. Finally, the combined effect of miR-139 and ATP7A/B on the chemoresistance of ovarian cancer cell was assessed. RESULTS:miR-139 expression was down-regulated in cisplatin-resistant ovarian cancer tissues (**P < 0.01) and reduced by cisplatin treatment in ovarian cell lines (*P < 0.05, **P < 0.01); miR-139 could enhance cisplatin-induced suppression on ovarian cancer cell viability, shown as reduced lC50 values; ATP7A and ATP7B protein levesincreased approximately 2 ~ fold-changein cisplatin-resistant cell lines. MiR-139 directly bound to the 3'UTR of ATP7A/B, respectively; miR-139 inhibition increased lC50 values whereas ATP7A/B knockdown reduced lC50 values of CAOV-3 and SNU119 cell lines under cisplatin treatment; the effect of miR-139 inhibition could be partially attenuated by ATP7A/B knockdown. CONCLUSIONS:MiR-139/ATP7A/B axis can be a reliable biomarker for ovarian cancer diagnosis, and may affect the chemoresistance of ovarian cancer to cisplatin-based chemotherapy; rescuing miR-139 expression thus to inhibit ATP7A/B might contribute to dealing with the chemoresistance of ovarian cancer.
Entities:
Keywords:
ATP7A; ATP7B; Chemoresistance; Cisplatin (cDDP); MiR-139; Ovarian cancer