|Table of Contents|

MicroRNA-125a-5p targets ribonucleotide reductase regulatory subunit M2 to inhibit cisplatin resistance of A549/DDP cells

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

Issue:
2023 02
Page:
227-234
Research Field:
Publishing date:

Info

Title:
MicroRNA-125a-5p targets ribonucleotide reductase regulatory subunit M2 to inhibit cisplatin resistance of A549/DDP cells
Author(s):
JIANG Yongjie1; 2; PANG Min1; 2; GONG Haiying1; 2; HUANG Yuyan1; 2; JIANG Li1; 2
1.Affiliated Hospital of North Sichuan Medical College，Sichuan Nanchong 637000，China;2.North Sichuan Medical College，Sichuan Nanchong 637000，China.
Keywords:
miR-125a-5p; RRM2; cisplatin; non-small cell lung cancer; drug resistance
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2023.02.006
Abstract:
Objective:To explore the influence of microRNA-125a-5p (miR-125a-5p) on the cisplatin sensitivity of A549/DDP cells in non-small cell lung cancer and its mechanism.Methods:The expression level of miR-125a-5p in non-small cell lung cancer tissues and adjacent tissues was analyzed through ENCORI online database.Besides,the expression levels of miR-125a-5p in human lung epithelial normal cells (BEAS-2B) and non-small cell lung cancer cell lines (A549,A549/DDP,and SK-MES-1) were detected through real-time quantitative PCR(RT-qPCR).The expression of ribonucleotide reductase regulatory subunit M2 (RRM2) in A549 and A549/DDP cells was detected through RT-qPCR and Western blot.Moreover,the targeted regulatory sequence of miR-125a-5p and RRM2 was analyzed by bioinformatics methods.The regulation of miR-125a-5p and RRM2 in A549/DDP cells was determined by double luciferase gene reporter assay and Western blot.The cell survival rate and half inhibitory concentration (IC50) were detected by cell counting kit (CCK-8),and the cell apoptosis rate was determined by flow cytometry.Results:The expression level of miR-125a-5p in non-small cell lung cancer tissues and cell lines was significantly decreased (P＜0.05).Compared with A549 cells,the expression level of RRM2 in A549/DDP cells was significantly increased (P＜0.05).The over-expression of miR-125a-5p partially restored the inhibitory effect of cisplatin on A549/DDP cells.As a result,the cell survival rate was significantly decreased (P＜0.05),while the apoptosis rate was significantly increased (P＜0.05).Double luciferase gene reporter assay confirmed that miR-125a-5p could achieve targeted combination with RRM2 (P＜0.05).The over-expression of RRM2 reversed the effect of miR-125a-5p on A549/DDP,and reduced the sensitivity of A549/DDP to cisplatin (P＜0.05).Conclusion:miR-125a-5p can partially restore the sensitivity of A549/DDP cells to cisplatin through the targeted down-regulation of RRM2 gene expression.

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Memo:
四川省科技计划项目（编号：2020YFS0572）；四川省医学会项目（编号：2021HR24）
Last Update: 1900-01-01