Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China.
Department of Ophthalmology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China.
Mol Med Rep. 2020 Oct;22(4):2645-2654. doi: 10.3892/mmr.2020.11367. Epub 2020 Jul 28.
Gastric cancer is one of the most common types of cancer worldwide, with a high incidence and mortality rate. MicroRNAs (miRs) play an important role in tumorigenesis, cell proliferation, migration, apoptosis and metastasis of cancer. The present study aimed to investigate the role and potential mechanism of miR‑204‑5p in gastric cancer. The mRNA expression levels of miR‑204‑5p in gastric cancer were determined by reverse transcription‑quantitative PCR. Cell proliferation was determined using Cell Counting Kit‑8 and colony formation assays. Flow cytometry analysis was performed to detect the cell apoptosis rate. Wound healing and Transwell assays were carried out to determine the cell migration and invasion rates, respectively. A putative binding site of miR‑204‑5p in the 3' untranslated region of human epidermal growth factor receptor 2 (HER‑2) was predicted using a bioinformatics algorithm and confirmed using a dual‑luciferase reporter assay. miR‑204‑5p levels were downregulated in gastric cancer cells. Overexpression of miR‑204‑5p significantly inhibited cell proliferation and decreased cell colony formation. Additionally, miR‑204‑5p decreased the migration and invasion rates of gastric cancer cells. Furthermore, an increased apoptotic rate was detected following overexpression of miR‑204‑5p, along with increased expression levels of Bax and decreased expression levels of Bcl‑2. HER‑2 was a direct target of miR‑204‑5p, and inhibition of HER‑2 acted as a tumor suppressor by inhibiting cell proliferation, migration and invasion, and promoting cell apoptosis, which was reversed by the inhibition of miR‑204‑5p expression. These results suggested that miR‑204‑5p could exert its anti‑tumor function by inhibiting cell proliferation, migration and invasion, and promoting cell apoptosis via regulation of HER‑2, which may be a potential therapeutic target for gastric cancer.
胃癌是全球最常见的癌症类型之一,具有较高的发病率和死亡率。微小 RNA(miRs)在肿瘤发生、细胞增殖、迁移、凋亡和转移中发挥重要作用。本研究旨在探讨 miR-204-5p 在胃癌中的作用及潜在机制。采用逆转录定量 PCR 检测胃癌中 miR-204-5p 的 mRNA 表达水平。采用细胞计数试剂盒-8 和集落形成实验检测细胞增殖。采用流式细胞术分析检测细胞凋亡率。采用划痕愈合和 Transwell 实验分别检测细胞迁移和侵袭率。采用生物信息学算法预测 miR-204-5p 在人表皮生长因子受体 2(HER-2)3'非翻译区的潜在结合位点,并通过双荧光素酶报告基因实验进行验证。miR-204-5p 在胃癌细胞中表达下调。过表达 miR-204-5p 可显著抑制细胞增殖,减少细胞集落形成。此外,miR-204-5p 降低了胃癌细胞的迁移和侵袭率。进一步检测发现,过表达 miR-204-5p 可增加细胞凋亡率,同时增加 Bax 的表达水平,降低 Bcl-2 的表达水平。HER-2 是 miR-204-5p 的直接靶基因,抑制 HER-2 可通过抑制细胞增殖、迁移和侵袭,促进细胞凋亡发挥肿瘤抑制作用,而 miR-204-5p 表达的抑制可逆转这种作用。这些结果表明,miR-204-5p 可能通过调节 HER-2 抑制细胞增殖、迁移和侵袭,促进细胞凋亡,发挥其抗肿瘤功能,可能成为胃癌的潜在治疗靶点。