MiR-425 involves in the development and progression of renal cell carcinoma by inhibiting E2F6
MiR-425 involves in the development and progression of renal cell carcinoma by inhibiting E2F6
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MiR-425通过抑制E2F6参与肾细胞癌的发生和进展
DOI：
10.26355/eurrev_201810_16040
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发表时间：
2018-10-01
影响因子：
3.3
通讯作者：
Zhang, W.
中科院分区：
文献类型：
--
作者：
Cai, Q.;Zhao, A.;Zhang, W.
目的：研究miR-425对肾透明细胞癌（ccRCA）细胞增殖和凋亡的影响，并探讨其作用机制。患者和方法：本研究共收集80对人肾透明细胞癌（ccRCA）和癌旁正常组织标本。人ccRCA细胞系（786- 0）和正常人肾细胞系（HK-2）用于细胞研究。分别在ccRCA组织和细胞中检测miR-425的表达水平。利用生物信息学方法预测miR-425的靶基因，并通过荧光素酶报告基因检测进行验证。结果：定量逆转录-聚合酶链反应（qRT-PCR）结果显示，miR-425在ccRCA组织和细胞中的表达明显降低。miR-425过表达后，786-O细胞的增殖能力和细胞周期明显受到抑制。G 0/G1期细胞百分比明显增加，S期和G2/M期细胞百分比明显减少。此外，在miR-425干预组中，凋亡细胞的数量显著增加。在线靶基因预测软件提示E2 F6是miR-425潜在的下游靶基因。RT-PCR、Western blotting和荧光素酶报告基因检测表明，miR-425对E2 F6的表达具有负调控作用。此外，后续实验表明E2 F6的上调可抑制miR-425对ccRCA细胞增殖和凋亡的抑制作用。结论：本研究证实了miR-425对ccRCA细胞增殖和凋亡的抑制作用。因此，miR-425/E2 F6轴有望成为ccRCA靶向治疗的靶点之一，
OBJECTIVE: To investigate the effect of miR-425 on the proliferation and apoptosis of clear cell renal carcinoma (ccRCA) cells, and to explore the underlying mechanism.PATIENTS AND METHODS: A total of 80 pairs of human clear cell renal carcinoma (ccRCA) and cancer-adjacent normal tissue samples were collected in this study. Human ccRCA cell line (786-O) and normal human kidney cell line (HK-2) were used in cellular research. The expression level of miR-425 was detected in ccRCA tissues and cells, respectively. Target genes of miR-425 were predicted by bioinformatics and verified by luciferase reporter gene assay. Moreover, the role of miR-425 in regulating E2F6 as well as its effect on the proliferation and apoptosis of ccRCA cells were detected.RESULTS: Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) results showed that the expression of miR-425 was significantly decreased in ccRCA tissues and cells. The proliferation ability and cell cycle of 786-O cells were significantly inhibited after miR-425 overexpression. The percentage of cells in G0/G1 phase was remarkably increased, while the percentage of cells in S and G2/M phases was significantly decreased. Besides, the number of apoptotic cells was significantly increased in the miR-425 intervention group. On-line target gene prediction software indicated that E2F6 was the potential downstream target gene of miR-425. RT-PCR, Western blotting and luciferase reporter gene assay demonstrated that the expression of E2F6 was negatively regulated by miR-425. In addition, subsequent experiments showed that the up-regulation of E2F6 could suppress the inhibitory effect of miR-425 on the proliferation and apoptosis of ccRCA cells.CONCLUSIONS: Our research demonstrated the inhibitory function of miR-425 in ccRCA. Therefore, the miR-425/E2F6 axis was expected to be one of the targets of ccRCA targeted therapy,