Phase I Clinical Trial Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, China; Department of Oncology, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong, China.
Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Exp Cell Res. 2024 Apr 15;437(2):114012. doi: 10.1016/j.yexcr.2024.114012. Epub 2024 Mar 31.
Ovarian cancer is one of the most common gynecological tumors worldwide. Despite the availability of multiple treatments for ovarian cancer, its resistance to chemotherapy remains a significant challenge. miRNAs play crucial roles in the initiation and progression of cancer by affecting processes such as differentiation, proliferation, and chemoresistance. According to microarray and qPCR analyses, miR-7704 is significantly downregulated in cisplatin-resistant cells compared to parental cells. In this study, we found that miR-7704 inhibited the proliferation and promoted cisplatin sensitivity of ovarian cancer cells in vitro and in vivo. Moreover, ectopic expression of miR-7704 had the same effect as IL2RB knockdown. Further mechanistic studies revealed that miR-7704 played an inhibitory role by regulating IL2RB expression to inactivate the AKT signaling pathway. Furthermore, IL2RB reversed the miR-7704 mediated resistance to cisplatin in ovarian cancer. Based on these findings, miR-7704 and IL2RB show the potential as novel therapeutic targets for ovarian cancer.
卵巢癌是全球最常见的妇科肿瘤之一。尽管有多种治疗卵巢癌的方法，但它对化疗的耐药性仍然是一个重大挑战。miRNAs 通过影响分化、增殖和化疗耐药性等过程，在癌症的发生和发展中发挥着关键作用。根据微阵列和 qPCR 分析，miR-7704 在顺铂耐药细胞中与亲本细胞相比显著下调。在这项研究中，我们发现 miR-7704 在体外和体内抑制卵巢癌细胞的增殖并促进顺铂敏感性。此外，miR-7704 的异位表达与 IL2RB 敲低具有相同的效果。进一步的机制研究表明，miR-7704 通过调节 IL2RB 表达来抑制 AKT 信号通路，从而发挥抑制作用。此外，IL2RB 逆转了 miR-7704 介导的卵巢癌细胞对顺铂的耐药性。基于这些发现，miR-7704 和 IL2RB 显示出作为卵巢癌新的治疗靶点的潜力。
