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Published on: March 30, 2019
Expression and Regulatory Network Analysis of Function of Small Nucleolar RNA Host Gene 4 in Hepatocellular Carcinoma
Jing Cao1, Cuicui Xiao2, Christ-Jonathan Tsia Hin Fong3
1Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Background And Aims:
Long non-coding RNA small nucleolar RNA host genes (SNHGs) play a critical role in the occurrence and development of tumors. In this study, we aimed to investigate the role of SNHG4 in hepatocellular carcinoma (HCC) and its underlining mechanism.
Methods:
Datasets were acquired from The Cancer Genome Atlas (TCGA) database. lncLocator 2.0 was used to identify the distribution of SNHG4 in HCC cells. Gene expression, Kaplan-Meier survival, microRNA and transcription factor target analyses were performed with the University of Alabama Cancer (UALCAN) Database, Kaplan-Meier Plotter, LinkedOmics, WebGestalt and gene set enrichment analysis, respectively. Gene Ontology and pathway enrichment analyses and assessment of RNA binding proteins were performed by R software, circlncRNAnet and Encyclopedia of RNA Interactomes (ENCORI). In addition, CirclncRNAnet and ENCORI were used to find the correlation between SNHG4 and important proteins, while the prognostic value was assessed with the Human Protein Atlas database and Kaplan-Meier Plotter.
Results:
Expression of SNHG4 in HCC is higher in HCC tissue than in normal healthy liver tissues and is mainly distributed in the nucleus. SNHG4 positively correlated with poor prognosis (p<0.01 for overall survival and recurrence-free survival). Functional enrichment analysis revealed SNHG4 involvement with regulation of ribosomal RNA synthesis and the RNA processing and surveillance pathway. SNHG4 is closely associated with miR-154 and miR-206, transcription factor target E2F family and the signaling pathway for MAPK/ERK and mTOR. U2 auxiliary factor 2 (U2AF2) showed strong correlation with SNHG4, while low-expression of U2AF2 showed good prognosis.
Conclusions:
Based on our findings, we infer SNHG4 may play a role in the formation of HCC via regulation of tumor-related pathways.
Insights
Long non-coding RNA SNHG4 is upregulated in hepatocellular carcinoma (HCC), correlating with poor prognosis. This suggests SNHG4 may drive HCC development through tumor-related pathways.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) are implicated in cancer development.
- Small nucleolar RNA host genes (SNHGs) are a class of lncRNAs with known roles in tumorigenesis.
- The specific role of SNHG4 in hepatocellular carcinoma (HCC) requires further investigation.
Purpose of the Study:
- To investigate the role of SNHG4 in hepatocellular carcinoma (HCC).
- To elucidate the underlying molecular mechanisms of SNHG4 in HCC.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) database for gene expression and survival analyses.
- Employed bioinformatics tools including lncLocator 2.0, UALCAN, Kaplan-Meier Plotter, LinkedOmics, WebGestalt, and R software for comprehensive analysis.
- Performed Gene Ontology, pathway enrichment, and RNA-binding protein interaction analyses.
Main Results:
- SNHG4 expression is significantly higher in HCC tissues compared to normal liver tissues.
- Elevated SNHG4 levels are associated with poorer overall survival and recurrence-free survival in HCC patients.
- Functional enrichment analysis indicated SNHG4's involvement in ribosomal RNA synthesis and RNA processing pathways.
- SNHG4 interacts with miR-154, miR-206, E2F transcription factors, and MAPK/ERK and mTOR signaling pathways.
- A strong correlation was observed between SNHG4 and U2 auxiliary factor 2 (U2AF2), with low U2AF2 expression predicting a better prognosis.
Conclusions:
- SNHG4 expression is upregulated in HCC and serves as a potential prognostic biomarker.
- SNHG4 may contribute to HCC development by regulating critical tumor-associated pathways.
- Further research into SNHG4's regulatory network could reveal novel therapeutic targets for HCC.
Related Concept Videos
lncRNA - Long Non-coding RNAs
Cell Specific Gene Expression
The Nucleolus
MicroRNAs
Regulation of Nuclear Protein Sorting
Regulation of Expression at Multiple Steps

