Department of Gynecology Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
FEBS Lett. 2012 May 7;586(9):1279-86. doi: 10.1016/j.febslet.2012.03.006. Epub 2012 Mar 27.
The mechanisms underlying ovarian cancer cell resistance to cisplatin (CDDP) are not fully understood. MicroRNAs (miRNAs) play important roles in tumorigenesis and drug resistance. In this paper, we utilized microRNA array and real-time PCR to show that miR-93 is significantly up-regulated in cisplatin-resistant ovarian cancer cells. In vitro assays show that over-expression and knock-down of miR-93 regulate apoptotic activity, and thereby cisplatin chemosensitivity, in ovarian cells. Furthermore, we found that miR-93 can directly target PTEN, and participates in the regulation of the AKT signaling pathway. MiR-93 inversely correlates with PTEN expression in CDDP-resistant and sensitive human ovarian cancer tissues. These results may have implications for therapeutic strategies aiming to overcome ovarian cancer cell resistance to cisplatin.
卵巢癌细胞对顺铂（CDDP）耐药的机制尚不完全清楚。microRNAs（miRNAs）在肿瘤发生和耐药中发挥重要作用。在本文中，我们利用 microRNA 阵列和实时 PCR 显示 miR-93 在顺铂耐药卵巢癌细胞中显著上调。体外实验表明，miR-93 的过表达和敲低调节了卵巢细胞的凋亡活性，从而调节了顺铂的化疗敏感性。此外，我们发现 miR-93 可以直接靶向 PTEN，并参与调节 AKT 信号通路。miR-93 在 CDDP 耐药和敏感的人卵巢癌组织中与 PTEN 表达呈负相关。这些结果可能对旨在克服卵巢癌细胞对顺铂耐药的治疗策略具有重要意义。
