MiR-221-3p通过靶向ERBB4降低卵巢癌细胞对顺铂的耐药性  

MiR-221-3p reduces cisplatin resistance in ovarian cancer cells by targeting ERBB4

作　　者：孙慧霞[1] 郭哲[1] 许静[1] 王青[1] 段运峥[1] 朱玲新 王启船 Sun Huixia;Guo Zhe;Xu Jing;Wang Qing;Duan Yunzheng;Zhu Lingxin;Wang Qichuan(No.1 Department of Special Need Gynecology,Nanyang City Center Hospital,Nanyang 473000,China;Department of Oncology,Nanyang Second People’s Hospital,Nanyang 473000,China)

机构地区：[1]河南省南阳市中心医院妇科特需一病区,南阳473000 [2]南阳市第二人民医院肿瘤科,南阳473000

出　　处：《中国组织化学与细胞化学杂志》2024年第5期413-419,共7页Chinese Journal of Histochemistry and Cytochemistry

基　　金：2022年河南省医学科技攻关联合共建项目(LHGJ20221051)。

摘　　要：目的探讨miR-221-3p在卵巢癌顺铂(cisplatin,DDP)耐药中的作用及相关机制。方法通过原位杂交组织化学染色观察顺铂耐药及敏感卵巢癌组织中miR-221-3p的表达;采用RT-qPCR检测顺铂耐药和敏感组织或细胞系中miR-221-3p的表达水平;评估过表达miR-221-3p后SKOV3/DDP细胞的增殖活力及凋亡水平;通过TargetScan进行信息学分析,预测miR-221-3p的潜在靶点,并通过双荧光素酶报告实验验证;检测过表达miR-221-3p和表皮生长因子受体4(epidermal growth factor receptor 4,ERBB4)后的SKOV3/DDP细胞增殖和凋亡。结果与顺铂敏感的组织或SKOV3细胞系相比,顺铂耐药的卵巢癌组织及SKOV3/DDP细胞系中miR-221-3p表达显著降低;与miR-NC组相比,miR-mimic组细胞在梯度浓度顺铂中的活力显著降低,且凋亡水平显著增加;TargetScan分析显示ERBB4为miR-221-3p的潜在靶点,双荧光素酶报告实验验证了该结果;与DDP+miR-mimic组相比,DDP+miR-mimic+pcDNA-ERBB4组细胞的凋亡水平显著减少。结论miR-221-3p可通过靶向ERBB4降低卵巢癌细胞对顺铂的耐药性。Objective To investigate the role of miR-221-3p in cisplatin(DDP)resistance in ovarian cancer and its underlying mechanisms.Methods In situ hybridization and immunohistochemical staining were used to observe the expression of miR-221-3p in cisplatin-resistant and-sensitive ovarian cancer tissues.RT-qPCR was performed to measure miR-221-3p expression levels in cisplatin-resistant and-sensitive tissues or cell lines.The effect of miR-221-3p overexpression on the proliferation and apoptosis of SKOV3/DDP cells was assessed.TargetScan was used for bioinformatic analysis to predict potential targets of miR-221-3p,which were then validated by dual-luciferase reporter assays.Proliferation and apoptosis levels of SKOV3/DDP cells were measured after overexpressing miR-221-3p and epidermal growth factor receptor 4(ERBB4).Results Compared to cisplatin-sensitive tissues or SKOV3 cell lines,miR-221-3p expression was significantly reduced in cisplatin-resistant ovarian cancer tissues and SKOV3/DDP cells.Compared to the miR-NC group,cells in the miR-mimic group showed significantly reduced viability in gradient concentrations of cisplatin,with a significant increase in apoptosis.TargetScan analysis predicted ERBB4 as a potential target of miR-221-3p,and this was confirmed by dual-luciferase reporter assays.Compared to the DDP+miR-mimic group,the DDP+miR-mimic+pcDNA-ERBB4 group showed a significant reduction in apoptosis.Conclusion miR-221-3p can reduce cisplatin resistance in ovarian cancer cells by targeting ERBB4.

关 键 词：miR-221-3p 表皮生长因子受体4 卵巢癌 顺铂 耐药 

分 类 号：R737.31[医药卫生—肿瘤]