microRNA-499a promotes the progression and chemoresistance of cervical cancer cells by targeting SOX6
microRNA-499a promotes the progression and chemoresistance of cervical cancer cells by targeting SOX6
复制标题
microRNA-499a通过靶向SOX6促进宫颈癌细胞的进展和化疗耐药
DOI：
10.1007/s10495-019-01588-y
复制
发表时间：
2020-04-01
期刊：
影响因子：
7.2
通讯作者：
Zou, Zhengzhi
中科院分区：
文献类型：
--
作者：
Chen, Yibing;Song, Yucen;Zou, Zhengzhi
Emerging evidence has indicated that microRNAs are involved in multiple processes of cancer development. Previous studies have demonstrated that microRNA-499a (miR-499a) plays both oncogenic and tumor suppressive roles in several types of malignancies, and genetic variants in miR-499a are associated with the risk of cervical cancer. However, the biological roles of miR-499a in cervical cancer have not been investigated. Quantitative real-time PCR was used to assess miR-499a expression in cervical cancer cells. Mimics or inhibitor of miR-499a was transfected into cervical cancer cells to upregulate or downregulate miR-499a expression. The effects of miR-499a expression change on cervical cancer cells proliferation, colony formation, tumorigenesis, chemosensitivity, transwell migration and invasion were assessed. The potential targets of miR-499a were predicted using online database tools and validated using real-time PCR, Western blot and luciferase reporter experiments. miR-499a was significantly upregulated in cervical cancer cells. Moreover, overexpression of miR-499a significantly enhanced the proliferation, cell cycle progression, colony formation, apoptosis resistance, migration and invasion of cervical cancer cells, while inhibiting miR-499a showed the opposite effects. Further exploration demonstrated that Sex-determining region Y box 6 was the direct target of miR-499a. miR-499a-induced SOX6 downregulation mediated the oncogenic effects of miR-499a in cervical cancer. Inhibiting miR-499a could enhance the anticancer effects of cisplatin in the xenograft mouse model of cervical cancer. Our findings for the first time suggest that miRNA-499a may play an important role in the development of cervical cancer and could serve as a potential therapeutic target.
