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Comprehensive upstream and downstream regulatory analyses identify miR-675-3p as a potential prognostic biomarker in melanoma

This study assessed miR-675-3p-related regulatory mechanisms in melanoma and the clinical relevance of such regulatory activities. We downloaded miRNA mature strand expression RNA-Seq, phenotypic, and DNA methylation data pertaining to the TCGA Melanoma cohort. Differentially expressed miRNAs (DEMs)...

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Autores principales: Zhao, Cai-Chou, Guo, Hao, Wang, Ying, Li, Jiu-Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Singapore 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900067/
https://www.ncbi.nlm.nih.gov/pubmed/33400243
http://dx.doi.org/10.1007/s13577-020-00473-0
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author Zhao, Cai-Chou
Guo, Hao
Wang, Ying
Li, Jiu-Hong
author_facet Zhao, Cai-Chou
Guo, Hao
Wang, Ying
Li, Jiu-Hong
author_sort Zhao, Cai-Chou
collection PubMed
description This study assessed miR-675-3p-related regulatory mechanisms in melanoma and the clinical relevance of such regulatory activities. We downloaded miRNA mature strand expression RNA-Seq, phenotypic, and DNA methylation data pertaining to the TCGA Melanoma cohort. Differentially expressed miRNAs (DEMs) between metastatic and primary melanoma patient tissues were then identified, and miR-675-3p expression in melanoma patient peripheral blood was confirmed using the GSE20994 GEO dataset, while its expression in melanoma cell lines was evaluated via qRT-RCR. The clinical and prognostic implications of miR-675-3p in melanoma were assessed, and miR-675-3p target genes were identified using bioinformatics tools. Functional roles of this miRNA were explored via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. We identified 3 and 22 miRNAs that were up- and downregulated, respectively, in metastatic melanoma samples relative to primary melanoma samples. Upregulation of miR-675-3p was associated with poorer overall patient survival, tumor histologic grade, and Clark's level. Consistently, miR-675-3p was also overexpressed in the peripheral blood of melanoma patients relative to healthy controls, and in melanoma cell lines relative to control cells. Gene regulatory networks indicated that 32 transcription factors control miR-675-3p expression, and that it, in turn, regulates 10 target genes. KEGG analyses indicated that these genes were associated with cell cycle, transcriptional misregulation in cancer, TGF-beta signaling, and HIF-1 signaling pathways. Gain-of-function assays revealed that miR-675-3p could promote cell proliferation via accelerating cell cycle progression. Western blotting results indicated that miR-675-3p could active TGF-beta and HIF-1 signaling. Through upstream and downstream analyses of miR-675-3p-related regulatory activity, we confirmed that this miRNA participates in key melanoma-related processes and offers value as a prognostic biomarker in melanoma patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13577-020-00473-0.
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spelling pubmed-79000672021-03-05 Comprehensive upstream and downstream regulatory analyses identify miR-675-3p as a potential prognostic biomarker in melanoma Zhao, Cai-Chou Guo, Hao Wang, Ying Li, Jiu-Hong Hum Cell Research Article This study assessed miR-675-3p-related regulatory mechanisms in melanoma and the clinical relevance of such regulatory activities. We downloaded miRNA mature strand expression RNA-Seq, phenotypic, and DNA methylation data pertaining to the TCGA Melanoma cohort. Differentially expressed miRNAs (DEMs) between metastatic and primary melanoma patient tissues were then identified, and miR-675-3p expression in melanoma patient peripheral blood was confirmed using the GSE20994 GEO dataset, while its expression in melanoma cell lines was evaluated via qRT-RCR. The clinical and prognostic implications of miR-675-3p in melanoma were assessed, and miR-675-3p target genes were identified using bioinformatics tools. Functional roles of this miRNA were explored via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. We identified 3 and 22 miRNAs that were up- and downregulated, respectively, in metastatic melanoma samples relative to primary melanoma samples. Upregulation of miR-675-3p was associated with poorer overall patient survival, tumor histologic grade, and Clark's level. Consistently, miR-675-3p was also overexpressed in the peripheral blood of melanoma patients relative to healthy controls, and in melanoma cell lines relative to control cells. Gene regulatory networks indicated that 32 transcription factors control miR-675-3p expression, and that it, in turn, regulates 10 target genes. KEGG analyses indicated that these genes were associated with cell cycle, transcriptional misregulation in cancer, TGF-beta signaling, and HIF-1 signaling pathways. Gain-of-function assays revealed that miR-675-3p could promote cell proliferation via accelerating cell cycle progression. Western blotting results indicated that miR-675-3p could active TGF-beta and HIF-1 signaling. Through upstream and downstream analyses of miR-675-3p-related regulatory activity, we confirmed that this miRNA participates in key melanoma-related processes and offers value as a prognostic biomarker in melanoma patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13577-020-00473-0. Springer Singapore 2021-01-05 2021 /pmc/articles/PMC7900067/ /pubmed/33400243 http://dx.doi.org/10.1007/s13577-020-00473-0 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Article
Zhao, Cai-Chou
Guo, Hao
Wang, Ying
Li, Jiu-Hong
Comprehensive upstream and downstream regulatory analyses identify miR-675-3p as a potential prognostic biomarker in melanoma
title Comprehensive upstream and downstream regulatory analyses identify miR-675-3p as a potential prognostic biomarker in melanoma
title_full Comprehensive upstream and downstream regulatory analyses identify miR-675-3p as a potential prognostic biomarker in melanoma
title_fullStr Comprehensive upstream and downstream regulatory analyses identify miR-675-3p as a potential prognostic biomarker in melanoma
title_full_unstemmed Comprehensive upstream and downstream regulatory analyses identify miR-675-3p as a potential prognostic biomarker in melanoma
title_short Comprehensive upstream and downstream regulatory analyses identify miR-675-3p as a potential prognostic biomarker in melanoma
title_sort comprehensive upstream and downstream regulatory analyses identify mir-675-3p as a potential prognostic biomarker in melanoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900067/
https://www.ncbi.nlm.nih.gov/pubmed/33400243
http://dx.doi.org/10.1007/s13577-020-00473-0
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