Wang Daohan, Cui He, Yan Yongjia, Fu Weihua, Lu Li
Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
Oncol Lett. 2025 Jan 15;29(3):143. doi: 10.3892/ol.2025.14889. eCollection 2025 Mar.
Chemoresistance is a major obstacle in the treatment of gastric cancer (GC). Notably, aberrant expression of microRNAs (miRs) is closely related to tumor development and progression. In the present study, the role of miR-424-5p in the chemoresistance of GC was investigated. Reverse transcription-quantitative PCR was used to detect the expression levels of miR-424-5p in tissues and different cell lines. Cell viability and apoptosis were detected via a Cell Counting Kit-8 assay, western blotting and flow cytometry. The targeting relationship between miR-424-5p and SMAD-specific E3 ubiquitin protein ligase 1 (SMURF1) was verified via dual-luciferase reporter assays and the molecular mechanism was investigated by western blotting. The results revealed that miR-424-5p was expressed at low levels in GC tissues and cell lines, and that low miR-424-5p expression was associated with poor N stage and worse prognosis, especially in patients who received adjuvant chemotherapy. Further experiments revealed that the overexpression of miR-424-5p reduced cisplatin (CDDP) resistance and promoted GC cell apoptosis, whereas inhibiting miR-424-5p had the opposite effect. Mechanistically, it was found that miR-424-5p downregulated the expression of SMURF1 to regulate the expression of ING2 and p53, thereby modulating CDDP resistance in GC. In summary, the present study demonstrated that miR-424-5p may serve an important regulatory role in CDDP resistance in GC, and could be a potential diagnostic biomarker and therapeutic target for GC chemoresistance.
化疗耐药是胃癌（GC）治疗中的主要障碍。值得注意的是，微小RNA（miR）的异常表达与肿瘤的发生发展密切相关。在本研究中，探讨了miR-424-5p在GC化疗耐药中的作用。采用逆转录定量PCR检测组织和不同细胞系中miR-424-5p的表达水平。通过细胞计数试剂盒-8检测、蛋白质印迹法和流式细胞术检测细胞活力和凋亡情况。通过双荧光素酶报告基因检测验证miR-424-5p与SMAD特异性E3泛素蛋白连接酶1（SMURF1）之间的靶向关系，并通过蛋白质印迹法研究其分子机制。结果显示，miR-424-5p在GC组织和细胞系中低表达，且低miR-424-5p表达与N分期差和预后较差相关，尤其是在接受辅助化疗的患者中。进一步实验表明，miR-424-5p过表达降低顺铂（CDDP）耐药性并促进GC细胞凋亡，而抑制miR-424-5p则产生相反的效果。机制上，发现miR-424-5p下调SMURF1的表达以调节ING2和p53的表达，从而调节GC中的CDDP耐药性。总之，本研究表明miR-424-5p可能在GC的CDDP耐药中起重要调节作用，并且可能是GC化疗耐药的潜在诊断生物标志物和治疗靶点。
