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Published on: May 21, 2019
Identification of miRNA-mRNA crosstalk in pancreatic cancer by integrating transcriptome analysis
1Department of Gastroenterology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China. yang_jian688@163.com.
Objective:
Pancreatic cancer is one of the most lethal diseases, and the pathogenesis remains largely unknown. To this end, we performed an integrated analysis of miRNA and mRNA expression data to explore the deregulation of miRNA and mRNA and regulatory processes underlying pancreatic cancer.
Materials And Methods:
We combined mRNA and miRNA expression data with miRNA target predictions to infer new miRNA regulation activities in pancreatic cancer. We first integrated miRNA and mRNA expression profiling separately to identify differently expressed miRNA and mRNA in pancreatic cancer. Then we adopted miRWalk databases prediction to obtain potential target genes of differently expressed miRNA, and compared these target genes to the gene list of integrated mRNA expression profiling to select differentially expressed miRNA-target gene whose expression was reversely correlated with that of corresponding miRNAs. Gene Ontology (GO) classification analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were employed to understand the functions and pathways of miRNA target genes. Finally we construct a miRNA-target gene regulatory network.
Results:
42 differentially expressed miRNAs, 1376 differentially expressed mRNAs were identified by combining three expression profiles of miRNA and mRNA separately in pancreatic cancer, 146 miRNA target genes were found in the gene list of integrated mRNA expression profiling based on bioinformatics prediction. Functional annotation was performed to understand the functions and pathways of miRNA target genes. Finally, we constructed a miRNA-target gene regulatory network including 206 miRNA-target gene pairs. Five miRNAs (hsa-miR-130b, hsa-miR-106b, hsa-miR-181c, hsa-miR-153 and hsa-miR-125a-5p) demonstrated the highest connectivities, whereas three miRNAs (MYC, E2F1 and IL6) were the mRNAs with the highest connectivities.
Conclusions:
Our findings may provide new insights into the knowledge of molecular mechanisms of pancreatic cancer and development of novel targeting therapies.
Insights
This study analyzed microRNA (miRNA) and messenger RNA (mRNA) expression in pancreatic cancer to uncover regulatory mechanisms. Key findings reveal specific miRNA-mRNA interactions that could lead to new therapeutic strategies for this lethal disease.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Pancreatic cancer is a highly lethal malignancy with poorly understood pathogenesis.
- MicroRNAs (miRNAs) and messenger RNAs (mRNAs) play crucial roles in cancer development.
- Understanding miRNA-mRNA regulatory networks is essential for identifying therapeutic targets.
Purpose of the Study:
- To investigate the deregulation of miRNA and mRNA expression in pancreatic cancer.
- To identify novel miRNA-mRNA regulatory interactions and pathways involved in pancreatic cancer.
- To construct a regulatory network for potential therapeutic insights.
Main Methods:
- Integrated analysis of miRNA and mRNA expression profiling data from pancreatic cancer.
- Utilized miRWalk database for miRNA target prediction and bioinformatics analysis.
- Identified differentially expressed miRNAs and mRNAs with inversely correlated expression.
- Performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.
- Constructed a miRNA-target gene regulatory network.
Main Results:
- Identified 42 differentially expressed miRNAs and 1376 differentially expressed mRNAs.
- Discovered 146 potential miRNA target genes and constructed a regulatory network with 206 miRNA-target gene pairs.
- Highlighted five highly connected miRNAs (hsa-miR-130b, hsa-miR-106b, hsa-miR-181c, hsa-miR-153, hsa-miR-125a-5p) and three highly connected mRNAs (MYC, E2F1, IL6).
Conclusions:
- The study provides new insights into the molecular mechanisms of pancreatic cancer.
- Identified key miRNA-mRNA interactions that may serve as novel targets for pancreatic cancer therapies.
- Findings contribute to the development of targeted therapeutic strategies for pancreatic cancer.
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