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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
An in silico analysis of dynamic changes in microRNA expression profiles in stepwise development of nasopharyngeal
Zhaohui Luo1, Liyang Zhang, Zheng Li
1Cancer Research Institute, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Carcinogenesis of Ministry of Health, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, P.R. China.
Background:
MicroRNAs (miRNAs) are small non-coding RNAs that participate in the spatiotemporal regulation of messenger RNA (mRNA) and protein synthesis. Recent studies have shown that some miRNAs are involved in the progression of nasopharyngeal carcinoma (NPC). However, the aberrant miRNAs implicated in different clinical stages of NPC remain unknown and their functions have not been systematically studied.
Methods:
In this study, miRNA microarray assay was performed on biopsies from different clinical stages of NPC. TargetScan was used to predict the target genes of the miRNAs. The target gene list was narrowed down by searching the data from the UniGene database to identify the nasopharyngeal-specific genes. The data reduction strategy was used to overlay with nasopharyngeal-specifically expressed miRNA target genes and complementary DNA (cDNA) expression data. The selected target genes were analyzed in the Gene Ontology (GO) biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway. The microRNA-Gene-Network was build based on the interactions of miRNAs and target genes. miRNA promoters were analyzed for the transcription factor (TF) binding sites. UCSC Genome database was used to construct the TF-miRNAs interaction networks.
Results:
Forty-eight miRNAs with significant change were obtained by Multi-Class Dif. The most enriched GO terms in the predicted target genes of miRNA were cell proliferation, cell migration and cell matrix adhesion. KEGG analysis showed that target genes were significantly involved in adherens junction, cell adhesion molecules, p53 signalling pathway et al. Comprehensive analysis of the coordinate expression of miRNAs and mRNAs reveals that miR-29a/c, miR-34b, miR-34c-3p, miR-34c-5p, miR-429, miR-203, miR-222, miR-1/206, miR-141, miR-18a/b, miR-544, miR-205 and miR-149 may play important roles on the development of NPC. We proposed an integrative strategy for identifying the miRNA-mRNA regulatory modules and TF-miRNA regulatory networks. TF including ETS2, MYB, Sp1, KLF6, NFE2, PCBP1 and TMEM54 exert regulatory functions on the miRNA expression.
Conclusions:
This study provides perspective on the microRNA expression during the development of NPC. It revealed the global trends in miRNA interactome in NPC. It concluded that miRNAs might play important regulatory roles through the target genes and transcription factors in the stepwise development of NPC.
Insights
This study identifies key microRNAs (miRNAs) and their regulatory networks involved in nasopharyngeal carcinoma (NPC) development. Understanding these miRNA roles offers new insights into NPC progression and potential therapeutic targets.
Area of Science:
- Molecular Biology
- Genomics
- Cancer Research
Background:
- MicroRNAs (miRNAs) are crucial regulators of gene expression.
- Aberrant miRNA expression is implicated in nasopharyngeal carcinoma (NPC) development.
- Systematic study of stage-specific miRNAs in NPC is lacking.
Purpose of the Study:
- To identify differentially expressed miRNAs in various clinical stages of NPC.
- To elucidate the functional roles of these miRNAs and their target genes in NPC.
- To construct regulatory networks involving miRNAs, target genes, and transcription factors.
Main Methods:
- miRNA microarray analysis of NPC biopsies.
- Bioinformatic prediction of miRNA targets using TargetScan and UniGene databases.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.
- Construction of miRNA-Gene-Networks and TF-miRNA interaction networks.
Main Results:
- Identified 48 significantly changed miRNAs in NPC.
- Enriched GO terms include cell proliferation, migration, and adhesion.
- KEGG analysis highlighted involvement in adherens junction and cell adhesion pathways.
- Key miRNAs (e.g., miR-29a/c, miR-34b, miR-141) and TFs (e.g., ETS2, MYB, Sp1) identified as critical in NPC development.
Conclusions:
- miRNAs play significant regulatory roles in the stepwise development of NPC.
- The study provides a global view of the miRNA interactome in NPC.
- Identified miRNA-mRNA modules and TF-miRNA networks offer insights into NPC pathogenesis.
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