MicroRNAs (miRNAs) play critical roles in the tumorigenesis and progression of gastric cancer (GC). However, the biological function of miR-4268 in GC and its mechanism remain unclear. In the present study, qTR-PCR found that the expression of miR-4268 was significantly downregulated in GC tissues and cell lines. The overexpression of miR-4268 inhibited GC cell proliferation and the cell cycle G1/S phase transition, and induced cell apoptosis. In contrast, inhibition of miR-4268 promoted cell proliferation and G1–S transition, and suppressed cell apoptosis. Further analyses revealed that miR-4268 expression was negatively correlated with Rab6B expression in GC tissues. Rab6B was verified to be a direct target of miR-4268. Notably, silencing Rab6B resulted in the same biological effects in GC cells as those induced by overexpression of miR-4268. Importantly, both miR-4268 overexpression and Rab6B silence inhibited the AKT/JNK signaling pathways, which modulated cell cycle regulators (Cyclin D1 and CDK4). In contrast, inhibition of miR-4268 promoted the AKT/JNK signaling pathways. MiR-4268 overexpression also promoted the p38 MAPK signaling pathway. Taken together, miR-4268 suppresses GC cell proliferation through inhibiting the AKT/JNK signaling pathways by targeting Rab6B and induces cell apoptosis through promoting the p38 MAPK signaling pathway. Our findings indicate a tumor-suppressor role of miR-4268 in GC pathogenesis and the potential of miR-4268 in GC theropy.

MicroRNA (miRNA) 在胃癌 (GC) 的肿瘤发生和进展中发挥着关键作用。然而，miR-4268在GC中的生物学功能及其机制仍不清楚。在本研究中，qTR-PCR发现miR-4268的表达在GC组织和细胞系中显着下调。miR-4268的过表达抑制GC细胞增殖和细胞周期G1/S期转变，并诱导细胞凋亡。相反，抑制 miR-4268 促进细胞增殖和 G1-S 转变，并抑制细胞凋亡。进一步分析发现GC组织中miR-4268的表达量与Rab6B的表达量呈负相关。Rab6B 被证实是 miR-4268 的直接靶标。值得注意的是，沉默 Rab6B 在 GC 细胞中产生的生物学效应与 miR-4268 过表达诱导的生物学效应相同。重要的是，miR-4268 过表达和 Rab6B 沉默都会抑制 AKT/JNK 信号通路，从而调节细胞周期调节因子（细胞周期蛋白 D1 和 CDK4）。相反，抑制 miR-4268 则促进 AKT/JNK 信号通路。MiR-4268 过表达还促进了 p38 MAPK 信号通路。综上所述，miR-4268通过靶向Rab6B抑制AKT/JNK信号通路来抑制GC细胞增殖，并通过促进p38 MAPK信号通路诱导细胞凋亡。我们的研究结果表明 miR-4268 在 GC 发病机制中的肿瘤抑制作用以及 miR-4268 在 GC 治疗中的潜力。