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Author Spotlight: Investigating Liver Cancer Pathogenesis Using Patient-Derived Organoids
Published on: August 18, 2023
Identification of downstream target genes regulated by CX43 in hepatocellular carcinoma
1Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.
Abstract:
The aim of study was to identify the downstream target genes of CX43 by Human Transcriptome Array. Therefore, a gene microarray was generated which consists of CX43-overexpressed hepatocellular carcinoma (HCC) cells transfected with the constructed plasmid and negative controls to identify candidate genes. Integrated bioinformatic analysis was used to clarify biological functions of the identified genes, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein-protein interaction network, and survival analysis. The candidate genes were further validated by qRT-PCR in liver cancer tissues and CX43-silenced HCC cells. We have found the mRNA and protein levels of CX43 significantly upregulated in HCC cells transfected with CX43 constructed plasmid. We identified 928 differentially expressed genes including 394 upregulated and 534 downregulated genes, enriched in the cancer related functions and pathways by GO and KEGG pathway analysis. The protein-protein interaction network revealed 9 hub genes in this study. Statistical analysis indicated that upregulation of RALA and SRC was associated with poor prognosis in liver cancer. The differential expression of 2 candidate genes were further validated in HCC cells and tissues. In conclusion, protein-coding genes RALA and SRC could be target genes of CX43 and therapeutic targets for hepatocellular carcinoma.
Insights
This study identifies RALA and SRC as downstream target genes of CX43 in hepatocellular carcinoma (HCC). Upregulation of these genes is linked to poor prognosis, suggesting potential therapeutic targets for liver cancer.
Area of Science:
- Molecular biology
- Genomics
- Oncology
Background:
- Hepatocellular carcinoma (HCC) is a major global health concern.
- Connexin 43 (CX43) plays a complex role in cancer, with its downstream targets in HCC requiring further elucidation.
Purpose of the Study:
- To identify downstream target genes of CX43 in hepatocellular carcinoma using transcriptomic analysis.
- To investigate the functional roles and prognostic significance of identified CX43 target genes in HCC.
Main Methods:
- Human Transcriptome Array for gene expression profiling of CX43-overexpressed HCC cells.
- Bioinformatic analyses including Gene Ontology (GO), KEGG pathway, and protein-protein interaction (PPI) network.
- Quantitative real-time PCR (qRT-PCR) for validation in HCC tissues and cell lines.
Main Results:
- CX43 overexpression significantly altered gene expression in HCC cells, identifying 928 differentially expressed genes.
- GO and KEGG analyses revealed enrichment in cancer-related pathways.
- RALA and SRC were identified as key hub genes and their upregulation correlated with poor prognosis in liver cancer patients.
Conclusions:
- CX43 influences hepatocellular carcinoma progression through downstream targets RALA and SRC.
- RALA and SRC represent potential therapeutic targets for improving outcomes in HCC.
- This study provides insights into the molecular mechanisms of CX43 in liver cancer.
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