Overexpression of miR‑424‑5p reduces cisplatin resistance by downregulating SMURF1 in gastric cancer.

Abstract

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.