miR-330调控TAp73α介导的结直肠癌细胞HCT116对顺铂的敏感性

TAp73α-mediated cisplatin sensitivity was suppressed by miR-330 in colorectal cancer cell HCT116

microRNA调控靶向基因的表达,影响其细胞周期进程、凋亡等过程的进行.采用双荧光素酶报告基因的方法,发现miR-330可以降低结合P73-3′UTR的荧光活性,同时在HCT116细胞中,慢病毒过表达miR-330可以抑制内源性TAp73蛋白的表达,在此基础上,用cisplatin处理细胞后,过表达miR-330的细胞加速凋亡,而这一过程在恢复TAp73的表达后,细胞凋亡活动又被减弱.另一方面,包装慢病毒shRNA-P73感染HCT116细胞所引起的生物学效应与miR-330一致.而且这种作用不依赖于p53.所以,在结肠癌细胞HCT116中,过表达miR-330可下调P73的表达并增强细胞对治疗药物顺铂的敏感性,为治疗顺铂抗性的肿瘤细胞提供了一条新途径.

microRNA could regulate the expression of targeted genes via influencing its cell cycle, apoptosis and other processes. P73-3＇UTR dual-luciferase activity could be decreased by overexpressing miR- 330. And endogenous TAp73 protein level could be downregulated via miR-330 overexpression by packaging lenti-virus. Meanwhile, apoptosis activities can be increased after cisplatin treatment in HCT116 cell lines stable expression miR-330. However, the process could be rescued by restoring the TAp73 expression, which is independent of p53. What＇s more, The same biological effects could be imitated by downregulating P73 protein level via packaging shRNA-P73. So TAp73a-mediated cisplatin sensitivity was suppressed by miR-330 in colorectal cancer cell HCT116, providing an effective strategy for therapeutic treatment of cisplatin-resistant cancer cells.