Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Department of Obstetrics and Gynecology, Tongren Hospital of Wuhan University (Wuhan Third Hospital), Wuhan, Hubei 430022, P.R. China.
Mol Med Rep. 2018 Nov;18(5):4381-4387. doi: 10.3892/mmr.2018.9452. Epub 2018 Sep 4.
Dicer is an essential enzyme that processes micro (mi)-RNA precursors into mature miRNAs, and serves a critical role in cancer development and progression by regulating gene expression. However, the role of Dicer in cisplatin‑mediated apoptosis and chemotherapy resistance in epithelial ovarian cancer (EOC) cells is poorly understood. In the present study, Dicer was expressed at low levels in cisplatin‑resistant A2780 cells when compared with parental cells. In addition, knocking down Dicer using short hairpin RNA decreased the sensitivity of A2780 and CAOV3 cells to cisplatin. Furthermore, downregulating Dicer significantly inhibited cisplatin‑induced apoptosis in ovarian cancer cells, and decreased the levels of proteins involved in apoptosis signaling pathways, including P73, P63, P53, caspase‑9 and caspase‑3. These findings indicated that Dicer may be a promising target for overcoming drug resistance in ovarian cancer.
Dicer 是一种重要的酶,可将 micro (mi)-RNA 前体加工成成熟的 miRNA,通过调节基因表达在癌症的发生和发展中起着关键作用。然而,Dicer 在顺铂介导的上皮性卵巢癌 (EOC) 细胞凋亡和化疗耐药中的作用尚不清楚。在本研究中,与亲本细胞相比,Dicer 在顺铂耐药的 A2780 细胞中表达水平较低。此外,使用短发夹 RNA 敲低 Dicer 可降低 A2780 和 CAOV3 细胞对顺铂的敏感性。此外,下调 Dicer 可显著抑制卵巢癌细胞中顺铂诱导的细胞凋亡,并降低凋亡信号通路相关蛋白的水平,包括 P73、P63、P53、caspase-9 和 caspase-3。这些发现表明,Dicer 可能是克服卵巢癌药物耐药性的一个有前途的靶点。