|Table of Contents|

miR-34a-5p enhances the sensitivity of cisplatin in cervical cancer cells and its possible mechanism

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 15
Page:
2688-2694
Research Field:
Publishing date:

Info

Title:
miR-34a-5p enhances the sensitivity of cisplatin in cervical cancer cells and its possible mechanism
Author(s):
JIA Yijuan; LIU Lidan; GONG Shixiong; LI Ling
Department of Gynecology,Wuhan No.1 Hospital,Hubei Wuhan 430022,China.
Keywords:
miR-34a-5p; cisplatin; cervical cancer; JAK/STAT3
PACS:
R737.33
DOI:
10.3969/j.issn.1672-4992.2024.15.002
Abstract:
Objective:To explore the effect of miR-34a-5p on cisplatin sensitivity of cervical cancer cells and its possible mechanism.Methods:Hela cells were treated with cisplatin at concentrations of 0,1,2,4 and 8 μg/mL respectively.Cell viability was detected by CCK8,and the expression of miR-34a-5p was detected by qRT-PCR.miR-34a-5p mimics were designed and synthesized,and the cells were divided into Blank,NC,miR-34a-5p,AG490 and miR-34a-5p+AG490 groups.Cell viability was detected by CCK8.Apoptosis rate was detected by flow cytometry.The number of invasive cells was detected by Transwell assay.The protein expression levels of MDM4,STAT3,MRP1,Bax and BCL-2 were detected by Western blot.Results：With the increase of cisplatin concentration,Hela cell viability and the expression of miR-34a-5p decreased gradually.After grouping,compared with the Blank/NC group,the cell viability,number of invasive cells,and the protein expression levels of MRP1,BCL-2,MDM4,p-STAT3/STAT3 in the miR-34a-5p and AG490 groups were decreased significantly (P＜0.05),while the apoptosis rate and Bax protein expression were increased significantly (P＜0.05).Compared with the miR-34a-5p/AG490 group,the cell viability,number of invasive cells,and the protein expression levels of MRP1,BCL-2,MDM4,p-STAT3/STAT3 in the miR-34a-5p+AG490 groups were decreased significantly (P＜0.05),while the apoptosis rate and Bax protein expression were increased significantly (P＜0.05).Conclusion：miR-34a-5p can increase the sensitivity of cervical cancer cells to cisplatin chemotherapy,and its mechanism may be related to MDM4/JAK/STAT3 signaling pathway.

References:

［1］FERLAY J,COLOMBET M,SOERJOMATARAM I,et al.Estimating the global cancer incidence and mortality in 2018:GLOBOCAN sources and methods［J］.Int J Cancer,2019,144(8):1941-1953.
［2］MADDAH SAFAEI A,ESMATI E,GOMAR M,et al.Hypofractionated versus standard chemoradiotherapy in the definitive treatment of uterine cervix cancer:interim results of a randomized controlled clinical trial［J］.J Cancer Res Clin Oncol,2024,150(1):20.
［3］SANTOS JMO,PEIXOTO DA SILVA S,COSTA NR, et al.The role of microRNAs in the metastatic process of high-risk HPV-induced cancers［J］.Cancers,2018,10(12):493.
［4］LARRUE R,FELLAH S,BOUKROUT N,et al.miR-92a-3p regulates cisplatin-induced cancer cell death［J］.Cell Death Dis,2023,14(9):603.
［5］LV T,SONG K,ZHANG L,et al.miRNA-34a decreases ovarian cancer cell proliferation and chemoresistance by targeting HDAC1［J］.Biochem Cell Biol,2018,96(5):663-671.
［6］GUTIRREZ-HOYA A,SOTO-CRUZ I.Role of the JAK/STAT pathway in cervical cancer:Its relationship with HPV E6/E7 oncoproteins［J］.Cells,2020,9(10):2297.
［7］YI SA,KIM GW,YOO J,et al.HP1γ sensitizes cervical cancer cells to cisplatin through the suppression of UBE2L3［J］.Int J Mol Sci,2020,21(17):5976.
［8］BHATTACHARJEE R,DEY T,KUMAR L,et al.Cellular landscaping of cisplatin resistance in cervical cancer［J］.Biomed Pharmacother,2022,153:113345.
［9］RANGA S,YADAV R,CHHABRA R,et al.Long non-coding RNAs as critical regulators and novel targets in cervical cancer:current status and future perspectives［J］.Apoptosis,2023,28(7-8):925-942.
［10］ANAND U,DEY A,CHANDEL AKS,et al. Cancer chemotherapy and beyond:Current status,drug candidates,associated risks and progress in targeted therapeutics［J］.Genes Dis,2022,10(4):1367-1401.
［11］KHAN SU,FATIMA K,AISHA S,et al.Unveiling the mechanisms and challenges of cancer drug resistance［J］.Cell Commun Signal,2024,22(1):109.
［12］WANG X,ZHAO Y,LU Q,et al.miR-34a-5p inhibits proliferation,migration,invasion and epithelial-mesenchymal transition in esophageal squamous cell carcinoma by targeting LEF1 and inactivation of the Hippo-YAP1/TAZ signaling pathway［J］.J Cancer,2020,11(10):3072-3081.
［13］AFTAB M,POOJARY SS,SESHAN V,et al.Urine miRNA signature as a potential non-invasive diagnostic and prognostic biomarker in cervical cancer［J］.Sci Rep,2021,11(1):10323.
［14］YANG X,SUN Q,SONG Y,et al.circHUWE1 exerts an oncogenic role in inducing DDP-resistant NSCLC progression depending on the regulation of miR-34a-5p/TNFAIP8［J］.Int J Genomics,2021,2021:3997045.
［15］WANG F,KONG L,PU Y,et al.Long noncoding RNA DICER1-AS1 functions in methylation regulation on the multi-drugresistance of osteosarcoma cells via miR-34a-5p and GADD45A［J］.Front Oncol,2021,11:685881.
［16］ZUO Y,ZHENG W,LIU J,et al.miR-34a-5p/PD-L1 axis regulates cisplatin chemoresistance of ovarian cancer cells［J］.Neoplasma,2020,67(1):93-101.
［17］AOKI Y,OCHIAI K,LIM S,et al.Phase Ⅲ study of cisplatin with or without S-1 in patients with stage Ⅳb,recurrent,or persistent cervical cancer［J］.Br J Cancer,2018,119(5):530-537.
［18］朱素丽,陈运昊,姚尖平,等.肉 桂醛调控CD44s/STAT3信号通路抑制胰腺癌细胞增殖和肿瘤细胞干性［J］.中国药理学通报,2022,38(05):676-683. ZHU SL,CHEN YH,YAO JP,et al.Cinnamaldehyde inhibits pancreatic cancer cell proliferation and stemness via modulation of CD44s/STAT3 signaling pathway［J］.Chinese Pharm Bullet,2022,38(05):676-683.
［19］毛万丽,李杰慧,冉立.宫颈 癌顺铂耐药研究进展［J］.现代肿瘤医学， 2021,29(16):2927－2932. MAO Wanli,LI Jiehui,RAN Li.Research progress on cisplatin resistance in cervical cancer［J］.Modern Oncology,2021,29(16):2927－2932.
［20］ZHOU H,LI J,HE Y,et al.SLC25A17 inhibits autophagy to promote triple-negative breast cancer tumorigenesis by ROS-mediated JAK2/STAT3 signaling pathway［J］.Cancer Cell Int,2024,24(1):85.
［21］谷蕾,张丽军,刘立芳,等.JAK/STAT信号通路抑制剂与肺癌 JAK/STAT信号通路抑制剂与肺癌［J］.现代肿瘤医学， 2018,26(02):314－317. GU Lei,ZHANG Lijun,LIU Lifang,et al.Inhibitors of JAK/STAT signaling pathway and lung cancer［J］.Modern Oncology,2018,26(02):314－317.
［22］HU Q,BIAN Q,RONG D,et al.JAK/STAT pathway:extracellular signals,diseases,immunity,and therapeutic regimens［J］.Front Bioeng Biotechnol,2023,11:1110765.
［23］ZHONG Y,LE F,CHENG J,et al.Triptolide inhibits JAK2/STAT3 signaling and induces lethal autophagy through ROS generation in cisplatin resistant SKOV3/DDP ovarian cancer cells［J］.Oncol Rep,2021,45(5):1-10.
［24］HE P,LIU XL,LOU YQ,et al.miR-34a-5p enhances the sensitivity of cervical cancer cells to oxaliplatin chemotherapy via targeting MDM4［J］.Clinical and Experimental Obstetrics & Gynecology,2022,49(2):54.
［25］ZHANG S,YAN Z,LI Y,et al.Structure-based discovery of MDM2/4 dual inhibitors that exert antitumor activities against MDM4-overexpressing cancer cells［J］.J Med Chem,2022,65(8):6207-6230.

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湖北省科技厅科技创新项目（编号：2021CFB576）
Last Update: 2024-06-28