Volume 44 Issue 12
Dec.  2023
Turn off MathJax
Article Contents
Yangyang LIAN, Hongping YUE, Ya DUAN, Hongwen HU, Fang LUO. The Role of miRNA-15a/16 in Regulating Bmi-1 Protein in Ovarian Cancer Resistance to Cisplatin Chemotherapy[J]. Journal of Kunming Medical University, 2023, 44(12): 25-31. doi: 10.12259/j.issn.2095-610X.S20231204
Citation: Yangyang LIAN, Hongping YUE, Ya DUAN, Hongwen HU, Fang LUO. The Role of miRNA-15a/16 in Regulating Bmi-1 Protein in Ovarian Cancer Resistance to Cisplatin Chemotherapy[J]. Journal of Kunming Medical University, 2023, 44(12): 25-31. doi: 10.12259/j.issn.2095-610X.S20231204

The Role of miRNA-15a/16 in Regulating Bmi-1 Protein in Ovarian Cancer Resistance to Cisplatin Chemotherapy

doi: 10.12259/j.issn.2095-610X.S20231204
  • Received Date: 2023-07-01
    Available Online: 2023-12-19
  • Publish Date: 2023-12-25
  •   Objective  To investigate the mechanisms of miRNA-15a and miRNA-16 in the process of reversing cisplatin resistance in ovarian cancer.   Methods  Human ovarian cancer cisplatin-resistant cell lines CoC1/DDP were transfected with miRNA-15a and miRNA-16 mimics and treated with cisplatin. qRT-PCR was used to detect the expression levels of miRNA-15a and miRNA-16 in normal CoC1/DDP cell group, cisplatin treated group, negative control group, miRNA-15a transfected group, miRNA-16 transfected group and overexpressed Bmi-1 plasmid. Western blot was used to detect the expression level of Bmi-1 in each group, CCK-8 and Annexin V/PI were used to detect cell survival and apoptosis, and γ-H2AX immunofluorescence was used to detect cell apoptosis.   Results  The CoC1/DDP ovarian cancer cell line shows low expression of miRNA-15a and miRNA-16, and high expression of Bmi-1 protein, which makes it resistant to cisplatin. When the levels of miRNA-15a and miRNA-16 are overexpressed, the Bmi-1 protein decreases(P < 0.05), leading to a decrease in cell survival rate(P < 0.05), a significant increase in DNA apoptosis(P < 0.05), and more severe DNA damage(P < 0.05). Overexpression of Bmi-1 plasmid can increase cell viability(P < 0.05) and reduce the rate of cell apoptosis(P < 0.05).   Conclusion  The Bmi-1 protein may be a target for the regulation of miRNA-15a and miRNA-16, and overexpression of miRNA-15a and miRNA-16 can increase the sensitivity of ovarian cancer cells to cisplatin by reducing the Bmi-1 protein. This provides a new idea for predicting molecular markers of cisplatin resistance in ovarian cancer and overcoming drug resistance targets in ovarian cancer.
  • loading
  • [1]
    Zohre M,Azita T,Safoura T,et al. Ovarian cancer in the world: Epidemiology and risk factors[J]. International Journal of Women,s Health,2019,11(1):287-299.
    [2]
    Valmiki S,Aid M A,Chaitou A R,et al. Extracellular matrix: A treasure trove in ovarian cancer dissemination and chemotherapeutic resistance[J]. Cureus,2021,13(3):e13864-13864.
    [3]
    Mylena O,Emma W,Kerry M,et al. Mechanisms of chemotherapy resistance in ovarian cancer[J]. Cancer Drug Resistance (Alhambra,Calif. ),2022,5(2):304-316.
    [4]
    Glasgow A M,Argenta P,Abrahante E J,et al. Biological insights into chemotherapy resistance in ovarian cancer[J]. International Journal of Molecular Sciences,2019,20(9):2131-2131. doi: 10.3390/ijms20092131
    [5]
    廉阳秧. 上皮性卵巢癌差异表达基因的生物信息学分析[D]. 昆明: 昆明医科大学, 2016.
    [6]
    Wu C,Zheng X,Li X,et al. Reduction of gastric cancer proliferation and invasion by miR-15a mediated suppression of Bmi-1 translation[J]. Oncotarget,2016,7(12):14522-14536. doi: 10.18632/oncotarget.7392
    [7]
    Penny S M. Ovarian cancer: An overview[J]. Radiol Technol,2020,91(6):561-575.
    [8]
    Liu Q,Novak M K,Pepin R M,et al. MicroRNA-mediated regulation of microRNA machinery controls cell fate decisions[J]. ELife,2021,10:e72289. doi: 10.7554/eLife.72289
    [9]
    Kabakov A V,Kazakov O V,Poveshchenko A F,et al. Correlation between structural transformations in mesenteric lymph nodes and the levels microRNA during polychemotherapy of breast cancer[J]. Bulletin of Experimental Biology and Medicine,2022,172(4):467-471. doi: 10.1007/s10517-022-05415-4
    [10]
    杨雷,魏丽军,王福花,等. miR-93-3p和CDC42在上皮性卵巢癌化疗耐药组织中的表达及临床意义[J]. 实用医学杂志,2020,36(9):1217-1222. doi: 10.3969/j.issn.1006-5725.2020.09.020
    [11]
    Kulkarni B,Kirave P,Gondaliya P,et al. Exosomal miRNA in chemoresistance,immune evasion,metastasis and progression of cancer[J]. Drug Discovery Today,2019,24(10):2058-2067. doi: 10.1016/j.drudis.2019.06.010
    [12]
    Bugra S T,Demet A,Betul C,et al. The expression levels of miRNA-15a and miRNA-16-1 in circulating tumor cells of patients with diffuse large B-cell lymphoma[J]. Molecular Biology Reports,2018,46(1):975-980.
    [13]
    Xu,P,Wang Y,Deng Z,et al. MicroRNA-15a promotes prostate cancer cell ferroptosis by inhibiting GPX4 expression[J]. Oncology Letters,2022,23(2):67. doi: 10.3892/ol.2022.13186
    [14]
    Chu J,Zhu Y,Liu Y,et al. E2F7 overexpression leads to tamoxifen resistance in breast cancer cells by competing with E2F1 at miR-15a/16 promoter[J]. Oncotarget,2015,6(31):31944-31957. doi: 10.18632/oncotarget.5128
    [15]
    Dhar K S D,Banerjee S M,Dahai J,et al. Therapeutic evaluation of microRNA-15a and microRNA-16 in ovarian cancer[J]. Oncotarget,2016,7(12):15093-15104. doi: 10.18632/oncotarget.7618
    [16]
    Dey A,Xiong X,Crim A,et al. Evaluating the mechanism and therapeutic potential of PTC-028,a novel inhibitor of BMI-1 function in ovarian cancer[J]. Molecular Cancer Therapeutics,2018,17(1):39-49. doi: 10.1158/1535-7163.MCT-17-0574
    [17]
    Xin T,Zhang F B,Sui G J,et al. Bmi-1 siRNA inhibited ovarian cancer cell line growth and decreased telomerase activity[J]. British Journal of Biomedical Science,2012,69(2):62-66. doi: 10.1080/09674845.2012.12002438
    [18]
    Zhang X L,Sun B L,Tian S X,et al. MicroRNA-132 reverses cisplatin resistance and metastasis in ovarian cancer by the targeted regulation on Bmi-1[J]. European Review for Medical and Pharmacological Sciences,2019,23(9):3635-3644.
    [19]
    Salem A,Hagen K,Silvia D,et al. Polycomb protein BMI-1 as a potential therapeutic target in mucinous ovarian cancer[J]. Anticancer Research,2022,42(4):1739-1747. doi: 10.21873/anticanres.15650
  • Relative Articles

    [1] Ran CHEN, Hechuan ZHANG, Yajing ZHANG, Liangji GUO, Hao ZHAO. Investigation on the Current Situation of Sexual Knowledge,Attitude and Behavior of College Students in Three Non-Medical Universities in Yunnan Province. Journal of Kunming Medical University, 2024, 45(8): 38-43.  doi: 10.12259/j.issn.2095-610X.S20240806
    [2] Lizhu ZHAO, Ying DONG, Yue DENG, Lihua YANG. Correlation between Epithelial Cell Related Genes and Prognosis of Patients with Ovarian Cancer based on Single Cell Sequencing. Journal of Kunming Medical University, 2024, 45(4): 9-16.  doi: 10.12259/j.issn.2095-610X.S20240402
    [3] Xingfen WANG, Yue DENG, Lihua YANG. Construction of Lipid Metabolism-Related Gene Prognostic Model and Immunoinfiltration Analysis of Ovarian Cancer. Journal of Kunming Medical University, 2024, 45(4): 17-25.  doi: 10.12259/j.issn.2095-610X.S20240403
    [4] Yaping JIANG, Hongying YANG, Haohan WANG, Xianling Ning, Xielan YANG. Effect of Different Intestinal Surgical Methods on Prognosis of Patients with Intestinal Invasive Epithelial Ovarian Cancer. Journal of Kunming Medical University, 2023, 44(1): 85-90.  doi: 10.12259/j.issn.2095-610X.S20230109
    [5] Rui CAO, Chang XU, Xiaomei JIN, Jie DAI, Huichao CHEN, Lijuan DONG, Min YANG, Li YANG, Min CHEN. Analysis of Recent Infections Among HIV-1 Infected MSM in Kunming City from 2018 to 2020. Journal of Kunming Medical University, 2022, 43(8): 150-155.  doi: 10.12259/j.issn.2095-610X.S20220825
    [6] Xiaoyan YANG, Chunguang HAO, Zhijian ZHANG. Mechanisms of Progesterone on Proliferation and Migration of Human Ovarian Cancer Cells via HOXA9. Journal of Kunming Medical University, 2022, 43(10): 35-42.  doi: 10.12259/j.issn.2095-610X.S20221022
    [7] Yue DENG, Dan ZOU, Abdelkerim Barh TOUNA, Lihua YANG. Expression of PDE4D Gene in Ovarian Cancer Based on Oncomine and the Regulation of Sanguinarine. Journal of Kunming Medical University, 2022, 43(3): 1-6.  doi: 10.12259/j.issn.2095-610X.S20220303
    [8] Lixiu XU, TUERXUN Meiliban, YAKUFU Kereman. Studies on Cisplatin Resistance of miR-181a in Ovarian Cancer Cells. Journal of Kunming Medical University, 2022, 43(1): 20-25.  doi: 10.12259/j.issn.2095-610X.S20220131
    [9] Zi-hong CHEN, Hong LIU, Ming-wei LIU, Mi SHU, Qiong NAN. Research Progress of miRNA-145 in Malignant Tumors of Digestive System. Journal of Kunming Medical University, 2021, 42(3): 145-148.  doi: 10.12259/j.issn.2095-610X.S20210334
    [10] Zhang Lu Ping , Zhang Long , Liu De Yu , Zhang Rui Ling , Feng Ling , Zhang Wen Jie , Han Yue Hong . Results of HIV/AIDS Surveillance among Men Who Have Sex with Men in Guandu District,Kunming City in 2013-2015. Journal of Kunming Medical University, 2017, 38(04): 132-136.
    [11] Hu Wan Qin , Zhao Hong Bo , Liang Hong , Zhao Qing Hua , Yang Li Hua . Analysis of Differential Expression Genes and Signal Pathways Associated with Cisplatin Resistant Ovarian Cancer. Journal of Kunming Medical University, 2017, 38(06): 97-101.
    [12] Hu Yu Chong , Lu Jing Kun , Cui Meng Yao . . Journal of Kunming Medical University, 2017, 38(03): 27-30.
    [13] Wang Chun Long , Han Dan , Wen Liang . Research Progress of Mesothelin in Tumor Diagnosis and Treatment. Journal of Kunming Medical University, 2017, 38(09): 134-139.
    [14] Wang Kun . Construction of ShRNA-Bmi1 Recombinant Vector and Its Effect on The Expression of hTERT in Transplantated Tumor of Nude Mice with Gallbladder Carcinoma. Journal of Kunming Medical University,
    [15] Yang Han . . Journal of Kunming Medical University,
    [16] Yan Zhi Mei . . Journal of Kunming Medical University,
    [17] Xie Xue Ni . . Journal of Kunming Medical University,
    [18] Fu Zhong Yang . . Journal of Kunming Medical University,
    [19] Qing Chen . . Journal of Kunming Medical University, 2013, 34(01): 1-3.
    [20] Yang Li Hua . . Journal of Kunming Medical University,
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(9)

    Article Metrics

    Article views (967) PDF downloads(10) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return