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An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma
Published on: April 17, 2013
Identification and interaction analysis of key miRNAs in medullary thyroid carcinoma by bioinformatics analysis
Lijie Zhang1, Donghui Lu1, Meiqin Liu1
1Tumor Diagnosis and Treatment Center, PLA 901 Hospital, Hefei, Anhui 230031, P.R. China.
Abstract:
Medullary thyroid carcinoma (MTC) is an endocrine tumor and comprises 5‑10% of all primary thyroid malignancies. However, the biomechanical contribution to the development and progression of MTC remains unclear. In this study, To discover the key microRNAs (miRNAs or miRs) and their potential roles in the tumorigenesis of MTC, the microarray datasets GSE97070, GSE40807 and GSE27155 were analyzed. The datasets were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed miRNAs (DEMs) and genes (DEGs) were accessed by R. Targets of DEMs and predicted using starBase, and functional and pathway enrichment analyses were performed using Metascape. A protein‑protein interaction (PPI) network and an analysis of modules were constructed using NetworkAnalyst. Finally, a network was constructed to show the regulatory association between transcription factors (TFs), DEMs and downstream genes. A total of 5 DEMs were found both in GSE97070 and GSE40807, including 3 upregulated DEMs and 2 downregulated DEMs. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses from Metascape revealed that the target genes of upregulated DEMs were significantly enriched in adherens junction, kinase and protein binding, while the target genes of downregulated DEMs were mainly involved in non‑canonical Wnt signaling pathway and RNA transport. From the PPI network, 13 nodes were screened as hub genes. Pathway enrichment analysis revealed that the top 5 modules were mostly enriched in the neurotrophin signaling pathway, mRNA surveillance pathway and MAPK signaling pathway. In addition, the TF‑DEMs‑target gene and DEGs regulatory network revealed that 17 TFs regulated 2 miRNAs, including upregulated or downregulated DEMs, CREB1 regulated all upregulated DEMs, and TGFB1 was an activator of hsa‑miR‑199a‑3p and a repressor of hsa‑miR‑429. Taken together, the present study identified several miRNAs and potential biological mechanisms involved in the tumorigenesis of MTC. This study identified the key DEMs and potential mechanisms underlying the development of MTC, and provided a series of biomarkers and targets for the management of MTC.
Insights
This study identifies key microRNAs (miRNAs) involved in medullary thyroid carcinoma (MTC) development. It reveals potential biomarkers and therapeutic targets for MTC management by analyzing gene expression data and regulatory networks.
Area of Science:
- Endocrinology
- Molecular Biology
- Genomics
Background:
- Medullary thyroid carcinoma (MTC) is a rare endocrine malignancy.
- The biomechanical factors influencing MTC development are not well understood.
- Identifying key molecular players in MTC tumorigenesis is crucial for effective management.
Purpose of the Study:
- To identify key microRNAs (miRNAs) and their roles in medullary thyroid carcinoma (MTC) tumorigenesis.
- To elucidate the regulatory networks and pathways associated with MTC development.
- To discover potential biomarkers and therapeutic targets for MTC.
Main Methods:
- Analysis of microarray datasets (GSE97070, GSE40807, GSE27155) from the Gene Expression Omnibus (GEO) database.
- Identification of differentially expressed miRNAs (DEMs) and genes (DEGs) using R.
- Prediction of miRNA targets, functional enrichment analysis (Gene Ontology, KEGG pathways), and protein-protein interaction (PPI) network construction.
Main Results:
- Five DEMs were identified, with 3 upregulated and 2 downregulated.
- Target genes of upregulated DEMs were enriched in adherens junction and protein binding pathways.
- Target genes of downregulated DEMs were associated with non-canonical Wnt signaling and RNA transport.
- Hub genes and key signaling pathways (neurotrophin, MAPK) were identified through PPI network analysis.
- A regulatory network revealed transcription factors (e.g., CREB1, TGFB1) regulating DEMs and target genes.
Conclusions:
- This study identified crucial miRNAs and biological mechanisms underlying MTC tumorigenesis.
- The findings provide potential biomarkers and therapeutic targets for MTC management.
- Understanding miRNA-mediated regulation offers new avenues for MTC treatment strategies.
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