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全面分析肝癌中部分上皮间质转化相关基因。

Comprehensive analysis of partial epithelial mesenchymal transition-related genes in hepatocellular carcinoma.

机构信息

Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

J Cell Mol Med. 2021 Jan;25(1):448-462. doi: 10.1111/jcmm.16099. Epub 2020 Nov 20.

Abstract

Increasing evidence has revealed that cancer cells undergoing an intermediate state, partial epithelial mesenchymal transition (p-EMT), tend to metastasize rather than complete EMT. We performed a comprehensive analysis of E-cadherin and 25 p-EMT-related genes in HCC to explore the roles and regulatory mechanisms of them in HCC. We analysed E-cadherin and 25 p-EMT-related genes in HCC and constructed an mRNA-miRNA-lncRNA ceRNA subnetwork containing p-EMT-related genes by bioinformatic approaches. IHC was used to identify the protein expression of key p-EMT-related genes, P4HA2, ITGA5, MMP9, MT1X and SPP1. Complete EMT is not necessary for HCC progression. Overexpression of P4HA2, ITGA5, MMP9, SPP1 and down-regulation of MT1X were found in HCC tissues, which were significantly associated with poor prognosis of HCC patients. By means of stepwise reverse prediction and validation from mRNA to lncRNA, an mRNA-miRNA-lncRNA ceRNA subnetwork correlated with HCC prognosis was identified by expression and survival analysis. This study implied that key p-EMT-related genes P4HA2, ITGA5, MMP9, MT1X, SPP1 could be prognostic biomarkers and potential targets of therapy for HCC patients. We constructed an mRNA-miRNA-lncRNA subnetwork containing p-EMT-related genes successfully, among which each component might be utilized as a prognostic biomarker of HCC.

摘要

越来越多的证据表明,处于中间状态的癌细胞,即部分上皮间质转化(p-EMT),更容易转移,而不是完全 EMT。我们对 HCC 中的 E-钙粘蛋白和 25 个 p-EMT 相关基因进行了全面分析,以探讨它们在 HCC 中的作用和调控机制。我们通过生物信息学方法分析了 HCC 中的 E-钙粘蛋白和 25 个 p-EMT 相关基因,并构建了一个包含 p-EMT 相关基因的 mRNA-miRNA-lncRNA ceRNA 子网络。免疫组织化学用于鉴定关键的 p-EMT 相关基因,如 P4HA2、ITGA5、MMP9、MT1X 和 SPP1 的蛋白表达。完全 EMT 对于 HCC 的进展并非必需。在 HCC 组织中发现 P4HA2、ITGA5、MMP9、SPP1 的过表达和 MT1X 的下调,这些与 HCC 患者的不良预后显著相关。通过从 mRNA 到 lncRNA 的逐步反向预测和验证,通过表达和生存分析,鉴定了一个与 HCC 预后相关的 mRNA-miRNA-lncRNA ceRNA 子网络。这项研究表明,关键的 p-EMT 相关基因 P4HA2、ITGA5、MMP9、MT1X、SPP1 可以作为 HCC 患者的预后标志物和潜在治疗靶点。我们成功构建了一个包含 p-EMT 相关基因的 mRNA-miRNA-lncRNA 子网络,其中每个成分都可能被用作 HCC 的预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1ac/7810929/7fbae364ef33/JCMM-25-448-g001.jpg

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