Shi Dazun, Tan Zhihui, Lu Rong, Yang Wenqing, Zhang Yi
Department of Obstetric and Gynaecology, Xiangya Hospital, Xiangya Hospital of Central South University, Changsha, China.
Department of Obstetric and Gynaecology, Xiangya Hospital, Xiangya Hospital of Central South University, Changsha, China.
Biochem Biophys Res Commun. 2014 Aug 8;450(4):1241-6. doi: 10.1016/j.bbrc.2014.06.094. Epub 2014 Jun 25.
MicroRNAs (miRNAs) are endogenous 19-25 nucleotide noncoding single-stranded RNAs that regulate gene expression by blocking the translation or decreasing the stability of mRNAs. In this study, we showed that miR-218 expression levels were decreased while Fbxw8 expression levels were increased in human choriocarcinoma cell lines, and identified Fbxw8 as a novel direct target of miR-218. Overexpression of miR-218 inhibited cell growth arrest at G2/M phase, suppressed the protein levels of cyclin A and up-regulated the expression levels of p27 through decreasing the levels of Fbxw8. On the other hand, forced expression of Fbxw8 partly rescued the effect of miR-218 in the cells, attenuated cell proliferation decrease the percentage of cells at G2/M phase, induced cyclin A protein expression and suppressed the protein level of p27 through up-regulating the levels of Fbxw8. Taken together, these findings will shed light the role to mechanism of miR-218 in regulating JEG-3 cells proliferation via miR-218/Fbxw8 axis, and miR-218 may serve as a novel potential therapeutic target in human choriocarcinoma in the future.
微小RNA（miRNA）是一类内源性的19 - 25个核苷酸的非编码单链RNA，通过阻断mRNA的翻译或降低其稳定性来调控基因表达。在本研究中，我们发现人绒毛膜癌细胞系中miR - 218表达水平降低，而Fbxw8表达水平升高，并确定Fbxw8是miR - 218的一个新的直接靶点。miR - 218的过表达抑制细胞在G2/M期的生长停滞，抑制细胞周期蛋白A的蛋白水平，并通过降低Fbxw8的水平上调p27的表达水平。另一方面，Fbxw8的强制表达部分挽救了miR - 218在细胞中的作用，减弱细胞增殖，降低G2/M期细胞的百分比，诱导细胞周期蛋白A的蛋白表达，并通过上调Fbxw8的水平抑制p27的蛋白水平。综上所述，这些发现将揭示miR - 218通过miR - 218/Fbxw8轴调控JEG - 3细胞增殖的作用机制，并且miR - 218未来可能成为人绒毛膜癌的一种新的潜在治疗靶点。
