Dataset Information

Construction of a ceRNA regulatory network to explore potential pathogenesis mechanisms involved in human hepatocellular carcinoma.

ABSTRACT: Worldwide, primary liver cancer is the third leading cause of cancer-related death. Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Recent studies have shown that circular RNAs (circRNAs) that interact with microRNAs (miRNAs) are involved in the occurrence and development of various tumours. Transcriptional profile analysis was used to analyse expression of circRNAs in HCC in this study. The top ten upregulated circRNAs were selected and validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in another 34 HCC patients. MiRNAs and mRNAs downstream of these circRNAs were explored through database analysis, and finally, the competitive endogenous RNA (ceRNA) networks were constructed for 5 selected circRNAs. We identified 9658 differentially expressed circRNAs by transcriptional profile analysis. QRT-PCR was performed to validate the top ten upregulated circRNAs, and five circRNAs were selected for further analysis. The miRNAs and mRNAs downstream of these five circRNAs were predicted to construct ceRNA network diagrams. Further analysis revealed five circRNA-miRNA-mRNA axes that correlate negatively with HCC prognosis. Numerous differentially expressed circRNAs exist in HCC, and they can regulate the biological behaviour of HCC through ceRNA networks. Bioinformatics analysis showed that ceRNA regulatory axes involved in HCC have high diagnostic and prognostic value and deserve further exploration.

SUBMITTER: Liu Y

PROVIDER: S-EPMC10716167 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Construction of a ceRNA regulatory network to explore potential pathogenesis mechanisms involved in human hepatocellular carcinoma.

Liu Yicun Y Dong Zhixing Z Chen WeiJie W Chen Lin L Ju Linling L Cai Weihua W Luo Xi X Bian Zhaolian Z

Scientific reports 20231212 1

Worldwide, primary liver cancer is the third leading cause of cancer-related death. Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Recent studies have shown that circular RNAs (circRNAs) that interact with microRNAs (miRNAs) are involved in the occurrence and development of various tumours. Transcriptional profile analysis was used to analyse expression of circRNAs in HCC in this study. The top ten upregulated circRNAs were selected and validated by quantitati ...[more]

PMID: 38086834

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Project description:Background: Circular RNAs (circRNAs) have been demonstrated to be closely related to the carcinogenesis of human cancer in recent years. However, the molecular mechanism of circRNAs in the pathogenesis of hepatocellular carcinoma (HCC) has not been fully elucidated. We aimed to identify critical circRNAs and explore their potential regulatory network in HCC. Methods: The robust rank aggregation (RRA) algorithm and weighted gene co-expression network analysis (WGCNA) were conducted to unearth the differentially expressed circRNAs (DEcircRNAs) in HCC. The expression levels of DEcircRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). A circRNA-miRNA-mRNA regulatory network was constructed by computational biology, and protein-protein interaction (PPI) network, functional enrichment analysis, survival analysis, and infiltrating immune cells analysis were performed to uncover the potential regulatory mechanisms of the network. Results: A total of 22 DEcircRNAs were screened out from four microarray datasets (GSE94508, GSE97332, GSE155949, and GSE164803) utilizing the RRA algorithm. Meanwhile, an HCC-related module containing 404 circRNAs was identified by WGCNA analysis. After intersection, only four circRNAs were recognized in both algorithms. Following qRT-PCR validation, three circRNAs (hsa_circRNA_091581, hsa_circRNA_066568, and hsa_circRNA_105031) were chosen for further analysis. As a result, a circRNA-miRNA-mRNA network containing three circRNAs, 17 miRNAs, and 222 mRNAs was established. Seven core genes (ESR1, BUB1, PRC1, LOX, CCT5, YWHAZ, and DDX39B) were determined from the PPI network of 222 mRNAs, and a circRNA-miRNA-hubgene network was also constructed. Functional enrichment analysis suggested that these seven hub genes were closely correlated with several cancer related pathways. Survival analysis revealed that the expression levels of the seven core genes were significantly associated with the prognosis of HCC patients. In addition, we also found that these seven hub genes were remarkably related to the infiltrating levels of immune cells. Conclusion: Our research identified three pivotal HCC-related circRNAs and provided novel insights into the underlying mechanisms of the circRNA-miRNA-mRNA regulatory network in HCC.

Project description:Long non-coding RNAs (lncRNAs) are among the most abundant types of non-coding RNAs in the genome and exhibit particularly high expression levels in the brain, where they play crucial roles in various neurophysiological and neuropathological processes. Although ischemic stroke is a complex multifactorial disease, the involvement of brain-derived lncRNAs in its intricate regulatory networks remains inadequately understood. In this study, we established a cerebral ischemia-reperfusion injury model using middle cerebral artery occlusion (MCAO) in male Sprague-Dawley rats. High-throughput sequencing was performed to profile the expression of cortical lncRNAs post-stroke, with subsequent validation using RT-PCR and qRT-PCR. Among the 31,183 lncRNAs detected in the rat cerebral cortex, 551 were differentially expressed between the MCAO and sham-operated groups in the ipsilateral cortex (fold change ≥2.0, P < 0.05). An integrated analysis of the 20 most abundant and significantly differentially expressed lncRNAs (DELs) identified 25 core cytoplasmic DELs, which were used to construct an interaction network based on their targeting relationships. This led to the establishment of a comprehensive lncRNA-miRNA-mRNA regulatory network comprising 12 lncRNAs, 16 sponge miRNAs, and 191 target mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that differentially expressed mRNAs (DEmRNAs) were significantly enriched in stroke-related pathways. Our analysis predicted four key lncRNAs, four miRNAs, and eleven crucial mRNAs involved in post-transcriptional regulation through competing endogenous RNA (ceRNA) mechanisms. These molecules were shown to participate extensively in post-stroke processes, including angiogenesis, axonal regeneration, inflammatory responses, microglial activation, blood-brain barrier (BBB) disruption, apoptosis, autophagy, ferroptosis, and thrombocytopenia. These findings highlight the role of lncRNAs as multi-level regulators in the complex network of post-stroke mechanisms, providing novel insights into the pathophysiological processes of stroke.

Dataset Information

Construction of a ceRNA regulatory network to explore potential pathogenesis mechanisms involved in human hepatocellular carcinoma.

Publications

Construction of a ceRNA regulatory network to explore potential pathogenesis mechanisms involved in human hepatocellular carcinoma.

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