Yang Shuli, Yang Ruiqi, Lin Ruixin, Si Lihui
Department of Obstetrics and Gynecology, Second Hospital of Jilin University, Changchun, 130041, P.R. China.
J BUON. 2019 Nov-Dec;24(6):2341-2346.
Ovarian cancer is responsible for a significant number of deaths in women and there is urgent need to develop efficient treatment strategies for this disease. Studies have shown microRNAs (miRs) are involved in diverse cellular processes and exhibit therapeutic implications. Herein, the role of miR-375 in ovarian cancer was explored.
OVACAR-3 cell line was mainly used in this research. Expression analysis was performed by qRT-PCR. Cell viability was determined by MTT assay. Cell cycle analysis was carried out by flow cytometry. Transwell assay was used for cell migration and invasion. Western blot analysis was used to determine the protein expression.
Gene expression analysis carried out by qRT-PCR of ovarian cancer cell lines and tissues revealed significant downregulation of miR-375. Ectopic expression of miR-375 halted the growth of the OVACAR-3 cells by triggering G2/M cell cycle arrest. Moreover, miR-375 also caused a significant decrease in the migratory and invasive potential of the OAVACAR-3 cells and enhanced their chemosensitivity to cisplatin. Bioinformatic analysis and the dual luciferase showed that miR-375 targets PAX2 in OVACAR-3 cells. Suppression of PAX2 inhibits the growth of the OVACAR-3 cells while PAX2 overexpression could avoid the growth inhibitory effects of miR-375 in OVACAR-3 cells.
miR-375 may prove to be an important therapeutic target in ovarian cancer and warrants further research endeavors.
卵巢癌导致大量女性死亡,迫切需要为该疾病开发有效的治疗策略。研究表明,微小RNA(miR)参与多种细胞过程并具有治疗意义。在此,探讨了miR-375在卵巢癌中的作用。
本研究主要使用OVACAR-3细胞系。通过qRT-PCR进行表达分析。通过MTT法测定细胞活力。通过流式细胞术进行细胞周期分析。Transwell实验用于检测细胞迁移和侵袭。蛋白质印迹分析用于测定蛋白质表达。
通过对卵巢癌细胞系和组织进行qRT-PCR基因表达分析,发现miR-375显著下调。miR-375的异位表达通过触发G2/M期细胞周期阻滞来阻止OVACAR-3细胞的生长。此外,miR-375还显著降低了OVACAR-3细胞的迁移和侵袭能力,并增强了它们对顺铂的化学敏感性。生物信息学分析和双荧光素酶实验表明,miR-375在OVACAR-3细胞中靶向PAX2。抑制PAX2可抑制OVACAR-3细胞的生长,而PAX2过表达可避免miR-375对OVACAR-3细胞的生长抑制作用。
miR-375可能是卵巢癌的一个重要治疗靶点,值得进一步研究。