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microRNA-499a promotes the progression and chemoresistance of cervical cancer cells by targeting SOX6

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Abstract

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.

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Acknowledgements

We would like to thank the Academy of Medical Sciences of Zhengzhou University Translational Medicine Platform for their kind help and support to this work.

Funding

This work was supported by the National Natural Science Foundation of China (81772643, 81772803, U1604172, 81702860, 81871877, 81402281 & 81402187), Henan College Innovation Support Program (18IRTSTHN024), Henan Medical Program (201602072 & 201701002) and Henan Science & Technology Program (172102310271). Scientific and Technological Planning Project of Guangzhou City (201805010002 and 201904010038).

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  1. Yibing Chen, Yucen Song and Yanjun Mi contributed equally to this work.

Authors and Affiliations

  1. Genetic and Prenatal Diagnosis Center, Department of Gynecology and Obstetrics, First Affiliated Hospital, Zhengzhou University, 1 Jianshe Road East, Zhengzhou, 450052, Henan, China

    Yibing Chen, Yucen Song, Jun Cao, Shumin Ren & Qian Ma

  2. Department of Medical Oncology, Cancer Hospital, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China

    Yanjun Mi

  3. Department of Gynecology and Obstetrics, First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, Henan, China

    Liping Han

  4. Department of Medical Oncology, First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, Henan, China

    Xiaofei Zhang

  5. MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, Guangdong, China

    Huan Jin, Haolong Li, Ting Huang & Zhengzhi Zou

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  1. Yibing Chen
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Chen, Y., Song, Y., Mi, Y. et al. microRNA-499a promotes the progression and chemoresistance of cervical cancer cells by targeting SOX6. Apoptosis 25, 205–216 (2020). https://doi.org/10.1007/s10495-019-01588-y

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