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长链非编码 RNA(lncRNA)MIR22HG 通过抑制 NOTCH2 信号通路抑制胃癌进展。

Long Noncoding RNA (lncRNA) MIR22HG Suppresses Gastric Cancer Progression through Attenuating NOTCH2 Signaling.

机构信息

Department of Digestive System, Beilun People's Hospital, Ningbo, Zhejiang, China (mainland).

Department of Pharmacology and Toxicology, Wright State University, Fairborn, OH, USA.

出版信息

Med Sci Monit. 2019 Jan 23;25:656-665. doi: 10.12659/MSM.912813.

Abstract

BACKGROUND Long noncoding RNAs (lncRNAs) are important regulators in human disease, including cancers. LncRNA MIR22HG has been shown to inhibit the progression of endometrial carcinoma, lung cancer, and hepatocellular carcinoma. Its role in gastric cancer is unclear. This study investigated MIR22HG effects on gastric cancer. MATERIAL AND METHODS Gastric cancer tissues (n=43) and adjacent normal tissues (n=21) were collected. Patients' 5-year overall survival rate was analyzed. Human normal gastric mucosal cell line (GES-1) and gastric cancer cell lines (MKN-45, AGS, SGC-7901) were cultured. AGS and MKN-45 cells were transfected by pcDNA3 empty vector, pcDNA3-MIR22HG overexpression vector, MIR22HG siRNA and its negative control, NOTCH2 siRNA and its negative control, respectively. Proliferation was explored by CCK-8 assay. Migration and invasion were explored by Transwell. qRT-PCR and western blot were used to investigate mRNA and proteins expression, respectively. RESULTS MIR22HG expression was decreased in gastric cancer tissues and cells (P<0.05). Low MIR22HG expression indicated lower 5-year overall survival rate (P<0.05). Upregulation of MIR22HG inhibited AGS and MKN-45 cell proliferation, migration and invasion (all P<0.05). Downregulation of MIR22HG elevated AGS and MKN-45 cell proliferation, migration, and invasion (all P<0.05). MIR22HG negatively regulated NOTCH2 signaling. Silencing MIR22HG elevated HEY1 and nucleus NOTCH2 expression. Silencing of NOTCH2 suppressed AGS and MKN-45 cells proliferation, migration and invasion (all P<0.05). CONCLUSIONS LncRNA MIR22HG suppressed gastric cancer progression through attenuating NOTCH2 signaling.

摘要

背景

长链非编码 RNA(lncRNA)是人类疾病(包括癌症)的重要调控因子。lncRNA MIR22HG 已被证明可抑制子宫内膜癌、肺癌和肝癌的进展。但其在胃癌中的作用尚不清楚。本研究探讨了 MIR22HG 对胃癌的影响。

方法

收集胃癌组织(n=43)和相邻正常组织(n=21)。分析患者的 5 年总生存率。培养人正常胃黏膜细胞系(GES-1)和胃癌细胞系(MKN-45、AGS、SGC-7901)。AGS 和 MKN-45 细胞分别转染 pcDNA3 空载体、pcDNA3-MIR22HG 过表达载体、MIR22HG siRNA 及其阴性对照、NOTCH2 siRNA 及其阴性对照。通过 CCK-8 法探讨增殖情况。通过 Transwell 探讨迁移和侵袭情况。qRT-PCR 和 Western blot 分别用于检测 mRNA 和蛋白表达。

结果

MIR22HG 在胃癌组织和细胞中表达降低(P<0.05)。MIR22HG 低表达提示 5 年总生存率较低(P<0.05)。上调 MIR22HG 抑制 AGS 和 MKN-45 细胞增殖、迁移和侵袭(均 P<0.05)。下调 MIR22HG 可提高 AGS 和 MKN-45 细胞的增殖、迁移和侵袭(均 P<0.05)。MIR22HG 负调控 NOTCH2 信号。沉默 MIR22HG 可提高 HEY1 和核 NOTCH2 表达。沉默 NOTCH2 可抑制 AGS 和 MKN-45 细胞的增殖、迁移和侵袭(均 P<0.05)。

结论

长链非编码 RNA MIR22HG 通过抑制 NOTCH2 信号抑制胃癌的进展。

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