ArticleFrontiers in immunology2022
Integrated analysis of transcription factor-mRNA-miRNA regulatory network related to immune characteristics in medullary thyroid carcinoma.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 6 citations in OpenAlex.
- Identification of miRNA-TF Regulatory Pathways Related to Diseases from a Neuroendocrine-Immune Perspective.Cellular and molecular neurobiology · 2024Article
- Decoding dynamic miRNA:ceRNA interactions unveils therapeutic insights and targets across predominant cancer landscapes.BioData mining · 2024Article
- Transcriptome Analyses Reveal the Important miRNAs Involved in Immune Response of Gastric Cancer.IET systems biologyArticle
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Medullary thyroid carcinoma (MTC), a thyroid C cell-derived malignancy, is poorly differentiated and more aggressive than papillary, follicular and oncocytic types of thyroid cancer. The current therapeutic options are limited, with a third of population suffering resistance. The differential gene expression pattern among thyroid cancer subtypes remains unclear. This study intended to explore the exclusive gene profile of MTC and construct a comprehensive regulatory network via integrated analysis, to uncover the potential key biomarkers. Methods: Multiple datasets of thyroid and other neuroendocrine tumors were obtained from GEO and TCGA databases. Differentially expressed genes (DEGs) specific in MTC were identified to construct a transcription factor (TF)-mRNA-miRNA network. The impact of the TF-mRNA-miRNA network on tumor immune characteristics and patient survival was further explored by single-sample GSEA (ssGSEA) and ESTIMATE algorithms, as well as univariate combined with multivariate analyses. RT-qPCR, cell viability and apoptosis assays were performed for in vitro validation. Results: We identified 81 genes upregulated and 22 downregulated in MTC but not in other types of thyroid tumor compared to the normal thyroid tissue. According to the L1000CDS2 database, potential targeting drugs were found to reverse the expressions of DEGs, with panobinostat (S1030) validated effective for tumor repression in MTC by in vitro experiments. The 103 DEGs exclusively seen in MTC were involved in signal release, muscle contraction, pathways of neurodegeneration diseases, neurotransmitter activity and related amino acid metabolism, and cAMP pathway. Based on the identified 15 hub genes, a TF-mRNA-miRNA linear network, as well as REST-cored coherent feed-forward loop networks, namely REST-KIF5C-miR-223 and REST-CDK5R2-miR-130a were constructed via online prediction and validation by public datasets and our cohort. Hub-gene, TF and miRNA scores in the TF-mRNA-miRNA network were related to immune score, immune cell infiltration and immunotherapeutic molecules in MTC as well as in neuroendocrine tumor of lung and neuroblastoma. Additionally, a high hub-gene score or a low miRNA score indicated good prognoses of neuroendocrine tumors. Conclusion: The present study uncovers underlying molecular mechanisms and potential immunotherapy-related targets for the pathogenesis and drug discovery of MTC.
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