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Published on: April 12, 2024
Identification of KHSRP-Regulated RNAs in Esophageal Cancer by Integrated Bioinformatics Analysis
1Department of Thoracic Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China.
Abstract:
The objective of this study was to identify key molecules that included long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs involved in esophageal cancer with KH-type splicing regulatory protein (KHSRP) knockdown. GSE99422 and GSE99423 from Gene Expression Omnibus database were extracted. After differentially expressed analysis of miRNAs, lncRNAs, and mRNAs, the lncRNAs-mRNAs interaction was obtained. Then the protein-protein interaction (PPI) network and module analyses were performed for differentially expressed mRNAs (DEmRNAs). Combined with miRWalk tool and DIANA-LncBase tool, regulating relationship between differentially expressed miRNAs (DEmiRNAs) and DEmRNAs/DElncRNAs were predicted. Finally, mRNA-miRNA-lncRNA regulatory network construction was established by Cytoscape software. Finally, the key genes were validated based on the Gene Expression Profiling Interactive Analysis (GEPIA) database. Totally, 2,027 DEmiRNAs, 3,480 DElncRNAs, and 18,293 DEmRNAs were screened. The PPI network included 399 nodes and 1671 interaction pairs, and two function models (Cluster 1 and Cluster 2) were separately identified. The PLK1 was a hub in the Cluster 1, which mainly enriched in the function of nuclear division. Then the competing endogenous RNA (ceRNA) network was constructed with 20 miRNAs, 66 lncRNA, and 202 mRNA. Here, lncRNA RP11-159D12.2 might function as a ceRNA in regulating BIRC5 expression of esophagus cancer through competitively binding to hsa-miR-4430. BIRC5 was mainly enriched in the function of mitotic nuclear division. Besides, the expression of BIRC5 and PLK1 genes was upregulated in tumor tissues compared with normal controls. Also, the correlation analysis showed that the key genes (BIRC5 and PLK1) were validated to be positively correlated with KHSRP. PLK1, BIRC5, hsa-miR-4430, and lncRNA RP11-159D12.2 were likely to be associated with esophageal cancer development.
Insights
KH-type splicing regulatory protein (KHSRP) knockdown in esophageal cancer revealed key molecules. PLK1 and BIRC5 genes, along with hsa-miR-4430 and lncRNA RP11-159D12.2, are implicated in cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Esophageal cancer is a significant global health concern.
- Understanding the molecular mechanisms underlying esophageal cancer is crucial for developing effective treatments.
- KH-type splicing regulatory protein (KHSRP) plays a role in cellular processes, but its specific involvement in esophageal cancer requires further elucidation.
Purpose of the Study:
- To identify key long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) involved in esophageal cancer following KHSRP knockdown.
- To construct a competing endogenous RNA (ceRNA) regulatory network to understand molecular interactions.
- To validate the expression and correlation of identified key molecules with KHSRP in esophageal cancer.
Main Methods:
- Data mining of Gene Expression Omnibus (GEO) datasets (GSE99422, GSE99423).
- Differential expression analysis of lncRNAs, miRNAs, and mRNAs.
- Protein-protein interaction (PPI) network and module analysis.
- Prediction of regulatory relationships using miRWalk and DIANA-LncBase tools.
- Construction of mRNA-miRNA-lncRNA regulatory network using Cytoscape.
- Validation of key genes using the Gene Expression Profiling Interactive Analysis (GEPIA) database.
Main Results:
- Identification of 2,027 differentially expressed miRNAs, 3,480 DElncRNAs, and 18,293 DEmRNAs.
- A PPI network revealed PLK1 as a hub gene in the nuclear division pathway.
- A ceRNA network was constructed, highlighting lncRNA RP11-159D12.2 potentially regulating BIRC5 expression via hsa-miR-4430.
- BIRC5 and PLK1 expression was upregulated in tumor tissues and positively correlated with KHSRP levels.
Conclusions:
- PLK1, BIRC5, hsa-miR-4430, and lncRNA RP11-159D12.2 are likely key molecules associated with esophageal cancer development.
- The identified ceRNA network provides insights into the molecular regulatory mechanisms in esophageal cancer.
- These findings suggest potential therapeutic targets for esophageal cancer treatment.
