Long noncoding RNA H19 participates in metformin-mediated inhibition of gastric cancer cell invasion

论文信息

题目：《Long noncoding RNA H19 participates in metformin-mediated inhibition of gastric cancer cell invasion》（译：《长非编码 RNA H19参与二甲双胍介导的胃癌细胞侵袭抑制》）
摘要：Recent research suggests that the first-line oral antidiabetes drug metformin may prevent gastric cancer progression and improve prognosis. Many studies have also shown that long noncoding RNAs (lncRNAs) play important roles in many biological processes. Therefore, we aimed to explore whether lncRNAs participate in the mechanisms by which metformin affects gastric cancer cells. In the current study, we found that metformin significantly inhibited the cellular functions of gastric cancer cells through Cell Counting Kit-8 and invasion assays. We found that lncRNA H19 was greatly downregulated in gastric cancer cells treated with metformin using lncRNA microassays. Based on bioinformatics analyses of the Oncomine and The Cancer Genome Atlas databases, H19 is shown to be overexpressed in gastric cancer tissues, with increased expression of H19 relating to advanced pathological tumor stage and pathological tumor node metastasis stage, indicating that H19 may be associated with the invasive ability of gastric cancer. We knocked down H19 in AGS and SGC7901 cell lines and found that knocked-down H19 could decrease gastric cancer cell invasion and that metformin could not further decrease invasion after the knock down. Moreover, H19 depletion increased AMPK activation and decreased MMP9 expression, and metformin could not further activate AMPK or decrease MMP9 in H19 knocked-down gastric cancer cells. In summary, metformin has a profound antitumor effect on gastric cancer cells, and H19 is a key component in the process of metformin suppressing gastric cancer cell invasion.（译：最近的研究表明，一线口服降糖药二甲双胍可预防胃癌进展，改善预后。许多研究也表明，长非编码rna（lncRNAs）在许多生物过程中起着重要作用。因此，我们旨在探讨lncRNAs是否参与二甲双胍影响胃癌细胞的机制。在本研究中，我们通过细胞计数Kit-8和侵袭实验发现二甲双胍显著抑制胃癌细胞的细胞功能。我们发现在二甲双胍治疗的胃癌细胞中，lncRNA H19的表达显著下调。根据对肿瘤和肿瘤基因组图谱数据库的生物信息学分析，H19在胃癌组织中过度表达，其表达增加与病理性肿瘤晚期和病理性肿瘤淋巴结转移期有关，提示H19可能与胃癌的侵袭能力有关。我们在AGS和SGC7901细胞系中敲除H19，发现敲除H19可以降低胃癌细胞的侵袭性，而二甲双胍不能进一步降低其侵袭性。此外，H19缺失增加了AMPK的活化，降低了MMP9的表达，二甲双胍不能进一步激活AMPK或降低H19敲除的胃癌细胞中的MMP9。综上所述，二甲双胍对胃癌细胞具有深远的抗肿瘤作用，而H19是二甲双胍抑制胃癌细胞侵袭过程中的关键成分。）
期刊：Journal of cellular physiology
Impact Factor: 3.923
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研究作者：李培文
研究单位：中国医科大学第一附属医院肿瘤外科
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