Department of Gastrointestinal Surgery, Affiliated Dongyang People's Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China.
Department of Operating Room, Affiliated Dongyang People's Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China.
Histol Histopathol. 2023 Jun;38(6):659-668. doi: 10.14670/HH-18-512. Epub 2022 Sep 12.
Gastric adenocarcinoma (GAC) caused by malignant transformation of gastric adenocytes is a malignancy with high incidence. MiR-195-5p modulates a variety of cancers. One of its target genes, orthodenticle homeobox 1 (OTX1), is believed to be a key modulator of tumor progression. We aim to analyze the mechanism of miR-195-5p and OTX1 in GAC. MiR-195-5p and OTX1 mRNA levels in GAC cells were tested via qRT-PCR. OTX1 protein and EMT-related protein levels were examined through western blot. Several cell functional assays were designed to measure changes in cell malignant behaviors. Dual luciferase assay verified the targeting relation of miR-195-5p and OTX1. These experimental results showed significantly low miR-195-5p expression and significantly high OTX1 expression in GAC cells. Enforced miR-195-5p level repressed cell malignant progression and accelerated cell apoptosis in GAC. Increased OTX1 weakened the above-mentioned effect caused by overexpressing miR-195-5p. Thus, miR-195-5p restrained migration, proliferation, invasion and epithelial-mesenchymal transition process of GAC cells, and promoted cell apoptosis through regulating OTX1. A new insight is provided for searching for biomarkers or therapeutic targets of GAC.
胃腺癌(Gastric adenocarcinoma,GAC)是由胃腺上皮恶性转化引起的恶性肿瘤,发病率较高。miR-195-5p 调节多种癌症。其靶基因之一同源异型盒 1(Orthodenticle homeobox 1,OTX1)被认为是肿瘤进展的关键调节剂。我们旨在分析 miR-195-5p 和 OTX1 在 GAC 中的作用机制。通过 qRT-PCR 检测 GAC 细胞中 miR-195-5p 和 OTX1 的 mRNA 水平。通过 Western blot 检测 OTX1 蛋白和 EMT 相关蛋白水平。设计了几种细胞功能测定来测量细胞恶性行为的变化。双荧光素酶报告基因实验验证了 miR-195-5p 和 OTX1 的靶向关系。这些实验结果表明,GAC 细胞中 miR-195-5p 表达明显降低,OTX1 表达明显升高。过表达 miR-195-5p 抑制了 GAC 中细胞恶性进展并加速了细胞凋亡。增加 OTX1 减弱了过表达 miR-195-5p 引起的上述作用。因此,miR-195-5p 通过调节 OTX1 抑制 GAC 细胞的迁移、增殖、侵袭和上皮-间充质转化过程,并促进细胞凋亡。为寻找 GAC 的生物标志物或治疗靶点提供了新的思路。