Department of Laparoscopic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116000, P.R. China.
CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, P.R. China.
Oncol Rep. 2019 Aug;42(2):745-752. doi: 10.3892/or.2019.7181. Epub 2019 Jun 3.
The present study was designed to identify the endogenous RNA regulatory networks involved in hepatocellular carcinoma (HCC) by bioinformatic analysis. Both miRNA interaction network‑based correlation analysis and expression‑based Spearman correlation coefficients were utilized to identify potential mRNA‑lncRNA interactions. Then, a competitive endogenous (ce)RNA network was constructed from these interactions, and network topology and Gene Ontology enrichment analyses were conducted to mine potential functions of ceRNAs. In HCC samples, a ceRNA network was constructed. It was composed of 35,657 edges connecting 113 lncRNAs and 6,136 mRNAs which were differentially expressed in HCC and normal liver tissues. Meanwhile, a number of significantly positively correlated mRNA and lncRNA pairs in this ceRNA network were found to be consistently positively correlated in another independent dataset. To be noted, further analyses on the potential roles of ceRNAs demonstrated than various lncRNAs such as LINC00657, TUG1 and SNHG1 may play key roles in HCC by regulating protein phosphorylation or cell cycle pathways or influencing miRNAs. From the perspective that lncRNAs can function as ceRNAs, this study revealed that the interaction between lncRNAs, miRNAs and mRNAs may provide new insight for the diagnosis and treatment in the tumorigenesis of hepatocellular carcinoma.
本研究旨在通过生物信息学分析鉴定参与肝细胞癌 (HCC) 的内源性 RNA 调控网络。本研究通过 miRNA 互作网络相关分析和基于表达的 Spearman 相关系数,鉴定潜在的 mRNA-lncRNA 相互作用。然后,从这些相互作用中构建竞争内源性 (ce)RNA 网络,并进行网络拓扑和基因本体 (GO) 富集分析,以挖掘 ceRNAs 的潜在功能。在 HCC 样本中,构建了 ceRNA 网络。该网络由 35657 个连接 HCC 和正常肝组织中差异表达的 113 个 lncRNA 和 6136 个 mRNA 的边组成。同时,在另一个独立数据集发现,该 ceRNA 网络中许多显著正相关的 mRNA 和 lncRNA 对在该数据集也呈一致的正相关。需要注意的是,进一步分析 ceRNAs 的潜在作用表明,各种 lncRNA,如 LINC00657、TUG1 和 SNHG1,可能通过调节蛋白磷酸化或细胞周期途径或影响 miRNAs 在 HCC 中发挥关键作用。从 lncRNA 可以作为 ceRNA 的角度来看,本研究揭示了 lncRNA、miRNA 和 mRNA 之间的相互作用可能为肝细胞癌的诊断和治疗提供新的思路。