MicroRNA-20a-5p inhibits the autophagy and cisplatin resistance in ovarian cancer via regulating DNMT3B-mediated DNA methylation of RBP1

被引:27
作者
Li, Hui [1 ]
Lei, Yuansheng [2 ]
Li, Shuangxue [3 ]
Li, Feng [4 ]
Lei, Jieyun [5 ]
机构
[1] Shanxi Prov Peoples Hosp, Gynaecol & Obstet, Taiyuan 030012, Shanxi, Peoples R China
[2] Shanxi Med Univ, Hosp 2, Internal Med Neurol, Taiyuan 030001, Shanxi, Peoples R China
[3] Shanxi Prov Peoples Hosp, Resp Med, Taiyuan 030012, Shanxi, Peoples R China
[4] Shanxi Med Univ, Gen Hosp Taigang, Dept Gen Surg, Taiyuan 030003, Shanxi, Peoples R China
[5] Shanxi Med Univ, Taiyuan Cent Hosp, Gynaecol & Obstet, Bldg 3,Wuyi Rd, Taiyuan 030010, Shanxi, Peoples R China
关键词
Ovarian cancer; MicroRNA-20a-5p; RBP1; DNMT3B; MIGRATION; INVASION; GROWTH;
D O I
10.1016/j.reprotox.2021.12.011
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Ovarian cancer (OvCa) is the third most common female malignancy worldwide and poses great threats on women health. Chemotherapy is the most recommended post-surgery treatment for OvCa patients; but, cisplatin resistance is a main cause of chemotherapy failure. In addition, autophagy modulates the sensitivity of tumor cells to chemotherapeutic agents. Hence, it is significant to explore the molecular mechanism concerning the autophagy and cisplatin resistance in OvCa. In this study, quantitative real-time PCR (qRT-PCR) was used to detect miR-20a-5p expression and western blot to measure RBP1 expression. A series of assays were conducted to explore the gain-of-function effects of miR-20a-5p. Luciferase reporter assay was applied to determine the downstream target of miR-20a-5p. The results proved that miR-20a-5p represses malignant phenotypes and autophagy in cisplatin-resistant OvCa cells. In addition, DNMT3B mediates DNA methylation of RBP1 to impair the promoting effects of RBP1 on carcinogenesis and autophagy in OvCa. Through rescue experiments, we certified that miR-20a-5p inhibits the autophagy and cisplatin resistance in OvCa via DNMT3B-mediated DNA methylation of RBP1. Collectively, we demonstrated that miR-20a-5p plays a crucial role in the modulation of autophagy and cisplatin resistance in OvCa, which might offer novel insights into developing effective treatment strategies for OvCa.
引用
收藏
页码:93 / 100
页数:8
相关论文
共 29 条
  • [1] DNA methylation in ovarian cancer - II. Expression of DNA methyltransferases in ovarian cancer cell lines and normal ovarian epithelial cells
    Ahluwalia, A
    Hurteau, JA
    Bigsby, RM
    Nephew, KP
    [J]. GYNECOLOGIC ONCOLOGY, 2001, 82 (02) : 299 - 304
  • [2] Epigenetic mechanisms and therapeutic targets of chemotherapy resistance in epithelial ovarian cancer
    Borley, Jane
    Brown, Robert
    [J]. ANNALS OF MEDICINE, 2015, 47 (05) : 359 - 369
  • [3] The RBP1-CKAP4 axis activates oncogenic autophagy and promotes cancer progression in oral squamous cell carcinoma
    Gao, Ling
    Wang, Qibo
    Ren, Wenhao
    Zheng, Jingjing
    Li, Shaoming
    Dou, Zhichao
    Kong, Xinjuan
    Liang, Xiao
    Zhi, Keqian
    [J]. CELL DEATH & DISEASE, 2020, 11 (06)
  • [4] Garzon R, 2009, ANNU REV MED, V60, P167, DOI [10.1146/annurev.med.59.053006.104707, 10.1146/annurev.pathol.4.110807.092222]
  • [5] MiR-20a-5p promotes radio-resistance by targeting Rab27B in nasopharyngeal cancer cells
    Huang, Dabing
    Bian, Geng
    Pan, Yueyin
    Han, Xinghua
    Sun, Yubei
    Wang, Yong
    Shen, Guodong
    Cheng, Min
    Fang, Xiang
    Hu, Shilian
    [J]. CANCER CELL INTERNATIONAL, 2017, 17
  • [6] RETRACTED: LncRNA PVT1 triggers Cyto-protective autophagy and promotes pancreatic ductal adenocarcinoma development via the miR-20a-5p/ULK1 Axis (Retracted article. See vol. 21, 2022)
    Huang, Fengting
    Chen, Wenying
    Peng, Juanfei
    Li, Yuanhua
    Zhuang, Yanyan
    Zhu, Zhe
    Shao, Chunkui
    Yang, Wanling
    Yao, Herui
    Zhang, Shineng
    [J]. MOLECULAR CANCER, 2018, 17
  • [7] High-Grade Serous Ovarian Cancer: Basic Sciences, Clinical and Therapeutic Standpoints
    Lisio, Michael-Antony
    Fu, Lili
    Goyeneche, Alicia
    Gao, Zu-hua
    Telleria, Carlos
    [J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2019, 20 (04)
  • [8] MiR-20a-5p regulates gemcitabine chemosensitivity by targeting RRM2 in pancreatic cancer cells and serves as a predictor for gemcitabine-based chemotherapy
    Lu, Huimin
    Lu, Shan
    Yang, Dujiang
    Zhang, Ling
    Ye, Jun
    Li, Mao
    Hu, Weiming
    [J]. BIOSCIENCE REPORTS, 2019, 39
  • [9] DAAM1-mediated migration and invasion of ovarian cancer cells are suppressed by miR-208a-5p
    Mei, Jie
    Huang, Yifu
    Hao, Leiyu
    Liu, Yan
    Yan, Ting
    Qiu, Tonglu
    Xu, Rui
    Xu, Bujie
    Xiao, Zhuang
    Jiang, Xiaozheng
    Hu, Kehan
    Zhu, Yichao
    [J]. PATHOLOGY RESEARCH AND PRACTICE, 2019, 215 (07)
  • [10] Ovarian cancer screening: Current status and future directions
    Nash, Zachary
    Menon, Usha
    [J]. BEST PRACTICE & RESEARCH CLINICAL OBSTETRICS & GYNAECOLOGY, 2020, 65 : 32 - 45