PMID- 31938895 OWN - NLM STAT- MEDLINE DCOM- 20210108 LR - 20210108 IS - 1573-675X (Electronic) IS - 1360-8185 (Linking) VI - 25 IP - 3-4 DP - 2020 Apr TI - microRNA-499a promotes the progression and chemoresistance of cervical cancer cells by targeting SOX6. PG - 205-216 LID - 10.1007/s10495-019-01588-y [doi] AB - 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. FAU - Chen, Yibing AU - Chen Y AD - Genetic and Prenatal Diagnosis Center, Department of Gynecology and Obstetrics, First Affiliated Hospital, Zhengzhou University, 1 Jianshe Road East, Zhengzhou, 450052, Henan, China. chenyibing@zzu.edu.cn. FAU - Song, Yucen AU - Song Y AD - Genetic and Prenatal Diagnosis Center, Department of Gynecology and Obstetrics, First Affiliated Hospital, Zhengzhou University, 1 Jianshe Road East, Zhengzhou, 450052, Henan, China. FAU - Mi, Yanjun AU - Mi Y AD - Department of Medical Oncology, Cancer Hospital, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China. FAU - Jin, Huan AU - Jin H AD - MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, Guangdong, China. FAU - Cao, Jun AU - Cao J AD - Genetic and Prenatal Diagnosis Center, Department of Gynecology and Obstetrics, First Affiliated Hospital, Zhengzhou University, 1 Jianshe Road East, Zhengzhou, 450052, Henan, China. FAU - Li, Haolong AU - Li H AD - MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, Guangdong, China. FAU - Han, Liping AU - Han L AD - Department of Gynecology and Obstetrics, First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, Henan, China. FAU - Huang, Ting AU - Huang T AD - MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, Guangdong, China. FAU - Zhang, Xiaofei AU - Zhang X AD - Department of Medical Oncology, First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, Henan, China. FAU - Ren, Shumin AU - Ren S AD - Genetic and Prenatal Diagnosis Center, Department of Gynecology and Obstetrics, First Affiliated Hospital, Zhengzhou University, 1 Jianshe Road East, Zhengzhou, 450052, Henan, China. FAU - Ma, Qian AU - Ma Q AD - Genetic and Prenatal Diagnosis Center, Department of Gynecology and Obstetrics, First Affiliated Hospital, Zhengzhou University, 1 Jianshe Road East, Zhengzhou, 450052, Henan, China. FAU - Zou, Zhengzhi AU - Zou Z AD - MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, Guangdong, China. zouzhengzhi@m.scnu.edu.cn. LA - eng GR - 81772803/National Natural Science Foundation of China/International GR - 81402187/National Natural Science Foundation of China/International PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Apoptosis JT - Apoptosis : an international journal on programmed cell death JID - 9712129 RN - 0 (MIRN499 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (SOX6 protein, human) RN - 0 (SOXD Transcription Factors) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Animals MH - Apoptosis MH - Cell Cycle MH - Cell Line, Tumor MH - Cell Movement MH - Cell Proliferation MH - Cisplatin/pharmacology/therapeutic use MH - *Drug Resistance, Neoplasm MH - Female MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Mice MH - MicroRNAs/antagonists & inhibitors/genetics/*metabolism MH - SOXD Transcription Factors/*genetics/metabolism MH - Uterine Cervical Neoplasms/genetics/metabolism/*pathology MH - Xenograft Model Antitumor Assays OTO - NOTNLM OT - Cell proliferation and invasion OT - Cervical cancer OT - Chemoresistance OT - Sex-determining region Y box 6 (SOX6) OT - miR-499a EDAT- 2020/01/16 06:00 MHDA- 2021/01/09 06:00 CRDT- 2020/01/16 06:00 PHST- 2020/01/16 06:00 [pubmed] PHST- 2021/01/09 06:00 [medline] PHST- 2020/01/16 06:00 [entrez] AID - 10.1007/s10495-019-01588-y [pii] AID - 10.1007/s10495-019-01588-y [doi] PST - ppublish SO - Apoptosis. 2020 Apr;25(3-4):205-216. doi: 10.1007/s10495-019-01588-y.