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综合生物信息学分析鉴定 lncRNA HCG22 为食管鳞癌细胞的迁移抑制剂。

Comprehensive bioinformatics analysis identifies lncRNA HCG22 as a migration inhibitor in esophageal squamous cell carcinoma.

机构信息

Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

J Cell Biochem. 2020 Jan;121(1):468-481. doi: 10.1002/jcb.29218. Epub 2019 Jun 25.

Abstract

Esophageal cancer is one of the most lethal malignancies worldwide, and esophageal squamous cell carcinoma (ESCC) is the dominant histological type. However, the long noncoding RNA (lncRNA) alterations in ESCC have not been elucidated to date. In this study, reliable databases from Gene Expression Omnibus (GEO), which analyzed lncRNA expression in ESCC tumor tissues and adjacent normal tissues were searched, and common differentially expressed lncRNAs and genes were analyzed. Next, cis- trans analysis was performed to predict the underlying relationships between altered lncRNAs and mRNAs, and the lncRNA-mRNA regulatory network was established. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of altered lncRNA-related genes were performed. The promising lncRNA HCG22 was validated by quantitative polymerase chain reaction (qPCR), and clinicopathological data were collected to identify the relationship between lncRNA HCG22 expression level and clinical features. Finally, Transwell assays were performed to explore the biological functions of lncRNA HCG22 in ESCC cells. Two hundred forty-one lncRNAs and 835 mRNAs were observed to be remarkably altered between ESCC tumor tissues and adjacent normal tissues. The lncRNA-mRNA regulatory network showed the coexpression association between lncRNA HCG22 and SPINK7 and ADAMTS12. GO and KEGG analyses showed that HCG22 and ADAMTS12 had potential biological functions in the cell migration of ESCC. The downregulation of lncRNA HCG22 in ESCC tumor tissues was validated by qPCR, and the clinicopathological data showed a noticeable correlation between lncRNA HCG22 expression level and the ESCC differentiational degree and clinical TNM stage. Kaplan-Meier analysis showed that patients with ESCC having low lncRNA HCG22 expression in ESCC tissues had considerably shorter overall survival compared with patients with ESCC having high lncRNA HCG22 expression. Following Transwell assays confirmed the migratory role of lncRNA HCG22 in ESCC cells. In conclusion, lncRNA HCG22 was downregulated in ESCC tissues and can be a migration inhibitor of ESCC cells, and SPINK7 and ADAMTS12 are promising to be the regulatory targets of lncRNA HCG22.

摘要

食管癌是全球最致命的恶性肿瘤之一,其中食管鳞状细胞癌(ESCC)是主要的组织学类型。然而,ESCC 的长链非编码 RNA(lncRNA)改变尚未得到阐明。在这项研究中,我们从基因表达综合数据库(GEO)中搜索了分析 ESCC 肿瘤组织和相邻正常组织中 lncRNA 表达的可靠数据库,并分析了常见的差异表达的 lncRNA 和基因。接下来,进行顺式-反式分析以预测改变的 lncRNA 和 mRNA 之间的潜在关系,并建立 lncRNA-mRNA 调控网络。对改变的 lncRNA 相关基因进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析。通过实时定量聚合酶链反应(qPCR)验证有前途的 lncRNA HCG22,并收集临床病理数据以确定 lncRNA HCG22 表达水平与临床特征之间的关系。最后,进行 Transwell 测定以探索 lncRNA HCG22 在 ESCC 细胞中的生物学功能。观察到 ESCC 肿瘤组织和相邻正常组织之间有 241 个 lncRNA 和 835 个 mRNA 显著改变。lncRNA-mRNA 调控网络显示 lncRNA HCG22 和 SPINK7 以及 ADAMTS12 之间存在共表达关联。GO 和 KEGG 分析表明 HCG22 和 ADAMTS12 在 ESCC 细胞迁移中具有潜在的生物学功能。通过 qPCR 验证了 lncRNA HCG22 在 ESCC 肿瘤组织中的下调,临床病理数据显示 lncRNA HCG22 表达水平与 ESCC 分化程度和临床 TNM 分期之间存在明显相关性。Kaplan-Meier 分析表明,ESCC 组织中 lncRNA HCG22 表达较低的 ESCC 患者的总生存期明显短于 lncRNA HCG22 表达较高的 ESCC 患者。随后的 Transwell 测定证实了 lncRNA HCG22 在 ESCC 细胞中的迁移作用。总之,lncRNA HCG22 在 ESCC 组织中下调,可作为 ESCC 细胞的迁移抑制剂,SPINK7 和 ADAMTS12 有望成为 lncRNA HCG22 的调节靶点。

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