Previous reports have shown that histone deacetylase inhibitors (HDACi) can alter miRNA expression in a range of cancers. Both the 5p-arm and 3p-arm of mature miRNAs can be expressed from the same precursor and involved in cancer progress. Nevertheless, the detailed mechanism by which vorinostat (SAHA), a HDACi, triggers miR-769–5p/miR-769-3p-mediated suppression of proliferation and induces apoptosis in gastric cancer (GC) cells remains elusive. Here, we showed that the miRNA-seq analysis of GC cells treated with SAHA identified seven differentially expressed miRNAs with both strands of the miRNA duplex. miR-769–5p/miR-769–3p expression was downregulated in GC tissues compared with normal tissues. Functionally, high expression of miR-769–5p/miR-769–3p blocked the malignant abilities of GC cells. Mechanistically, miR-769–5p/miR-769–3p targeted IGF1R and IGF1R overexpression rescued the effects of miR-769–5p/miR-769–3p on GC cells growth and metastasis. Moreover, STAT3 bound to the promoter of miR-769. Furthermore, miR-769–5p/miR-769–3p expression was negatively regulated by the STAT3-IGF1R-HDAC3 complex. Besides, miR-769–5p/miR-769–3p synergized with SAHA to promote GC cells apoptosis. Our studies suggest that miR-769–5p/miR-769–3p acts as a tumor suppressor by the STAT3-IGF1R-HDAC3 complex. Moreover, SAHA triggers miR-769–5p/miR-769-3p-mediated inhibition of proliferation and induces apoptosis in GC cells.

先前的报告表明，组蛋白去乙酰化酶抑制剂 (HDACi) 可以改变一系列癌症中的 miRNA 表达。成熟 miRNA 的 5p-arm 和 3p-arm 都可以从相同的前体表达并参与癌症进展。然而，伏立诺他 (SAHA)（一种 HDACi）触发 miR-769-5p/miR-769-3p 介导的增殖抑制并诱导胃癌 (GC) 细胞凋亡的详细机制仍然难以捉摸。在这里，我们展示了用 SAHA 处理的 GC 细胞的 miRNA-seq 分析鉴定了 7 个具有 miRNA 双链体两条链的差异表达的 miRNA。与正常组织相比，胃癌组织中 miR-769-5p/miR-769-3p 的表达下调。在功能上，miR-769-5p/miR-769-3p的高表达阻断了GC细胞的恶性能力。从机制上讲，miR-769-5p/miR-769-3p 靶向 IGF1R 和 IGF1R 过表达挽救了 miR-769-5p/miR-769-3p 对 GC 细胞生长和转移的影响。此外，STAT3 与 miR-769 的启动子结合。此外，miR-769-5p/miR-769-3p 表达受到 STAT3-IGF1R-HDAC3 复合物的负调控。此外，miR-769-5p/miR-769-3p与SAHA协同促进GC细胞凋亡。我们的研究表明 miR-769-5p/miR-769-3p 通过 STAT3-IGF1R-HDAC3 复合物充当肿瘤抑制因子。此外，SAHA 触发 miR-769-5p/miR-769-3p 介导的增殖抑制并诱导 GC 细胞凋亡。miR-769-5p/miR-769-3p 表达受到 STAT3-IGF1R-HDAC3 复合物的负调控。此外，miR-769-5p/miR-769-3p与SAHA协同促进GC细胞凋亡。我们的研究表明 miR-769-5p/miR-769-3p 通过 STAT3-IGF1R-HDAC3 复合物充当肿瘤抑制因子。此外，SAHA 触发 miR-769-5p/miR-769-3p 介导的增殖抑制并诱导 GC 细胞凋亡。miR-769-5p/miR-769-3p 表达受到 STAT3-IGF1R-HDAC3 复合物的负调控。此外，miR-769-5p/miR-769-3p与SAHA协同促进GC细胞凋亡。我们的研究表明 miR-769-5p/miR-769-3p 通过 STAT3-IGF1R-HDAC3 复合物充当肿瘤抑制因子。此外，SAHA 触发 miR-769-5p/miR-769-3p 介导的增殖抑制并诱导 GC 细胞凋亡。