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A Novel miRNA–mRNA Axis Involves in Regulating Transcriptional Disorders in Pancreatic Adenocarcinoma
BACKGROUND: Currently, there is still a lack of understanding about the mechanism and therapeutic targets of pancreatic adenocarcinoma (PAAD). The potential of miRNA–mRNA networks for the identification of regulatory mechanisms involved in PAAD development remains unexplored. METHODS: We compared di...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349199/ https://www.ncbi.nlm.nih.gov/pubmed/34377019 http://dx.doi.org/10.2147/CMAR.S316935 |
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author | Shang, Xin Shi, Lan-Er Taule, Dina Zhu, Zhang-Zhi |
author_facet | Shang, Xin Shi, Lan-Er Taule, Dina Zhu, Zhang-Zhi |
author_sort | Shang, Xin |
collection | PubMed |
description | BACKGROUND: Currently, there is still a lack of understanding about the mechanism and therapeutic targets of pancreatic adenocarcinoma (PAAD). The potential of miRNA–mRNA networks for the identification of regulatory mechanisms involved in PAAD development remains unexplored. METHODS: We compared differentially expressed miRNAs (DEMIs) and differentially expressed genes (DEGs) in PAAD and normal tissues from the Gene Expression Omnibus (GEO) database. Transcription factors (TFs) were obtained from FunRich. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs and DEMIs were implemented using Database for Annotation, Visualization and Integrated Discovery (DAVID). Then, key miRNAs and targeted mRNAs were identified by assessment of their expression and prognosis in UALCAN and Kaplan–Meier plotters. In the last step, the candidate miRNA–mRNA selected was confirmed by real-time quantitative polymerase chain reaction (qRT-PCR). RESULTS: We distinguished 62 significant DEMIs, 1314 upregulated DEGs, and 1110 downregulated DEGs. The top 10 TFs were identified. In total, there were 160 hub genes obtained by intersecting the set of 2224 predicted targets with the set of significant DEGs. And we selected 8 key miRNAs. Furthermore, low expression of miR-455-3p in PAAD tissue was closely connected with poor prognosis, and only 5 target mRNAs were predicted to be increased in PAAD tissue with poor prognosis. Therefore, a novel miRNA–hub gene regulatory network in PAAD was constructed. Finally, in vitro experiments indicated that miR-455-3p expression was decreased in PAAD sample. HOXC4, DLG4, DYNLL1 and FBXO45 were validated by qRT-PCR as highly probable targets of miR-455-3p. CONCLUSION: A novel miRNA–mRNA axis has been discovered that may be involved in the regulation of transcriptional disorders and affected the survival of PAAD patients, which would provide a novel strategy for the treatment of PAAD. |
format | Online Article Text |
id | pubmed-8349199 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-83491992021-08-09 A Novel miRNA–mRNA Axis Involves in Regulating Transcriptional Disorders in Pancreatic Adenocarcinoma Shang, Xin Shi, Lan-Er Taule, Dina Zhu, Zhang-Zhi Cancer Manag Res Original Research BACKGROUND: Currently, there is still a lack of understanding about the mechanism and therapeutic targets of pancreatic adenocarcinoma (PAAD). The potential of miRNA–mRNA networks for the identification of regulatory mechanisms involved in PAAD development remains unexplored. METHODS: We compared differentially expressed miRNAs (DEMIs) and differentially expressed genes (DEGs) in PAAD and normal tissues from the Gene Expression Omnibus (GEO) database. Transcription factors (TFs) were obtained from FunRich. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs and DEMIs were implemented using Database for Annotation, Visualization and Integrated Discovery (DAVID). Then, key miRNAs and targeted mRNAs were identified by assessment of their expression and prognosis in UALCAN and Kaplan–Meier plotters. In the last step, the candidate miRNA–mRNA selected was confirmed by real-time quantitative polymerase chain reaction (qRT-PCR). RESULTS: We distinguished 62 significant DEMIs, 1314 upregulated DEGs, and 1110 downregulated DEGs. The top 10 TFs were identified. In total, there were 160 hub genes obtained by intersecting the set of 2224 predicted targets with the set of significant DEGs. And we selected 8 key miRNAs. Furthermore, low expression of miR-455-3p in PAAD tissue was closely connected with poor prognosis, and only 5 target mRNAs were predicted to be increased in PAAD tissue with poor prognosis. Therefore, a novel miRNA–hub gene regulatory network in PAAD was constructed. Finally, in vitro experiments indicated that miR-455-3p expression was decreased in PAAD sample. HOXC4, DLG4, DYNLL1 and FBXO45 were validated by qRT-PCR as highly probable targets of miR-455-3p. CONCLUSION: A novel miRNA–mRNA axis has been discovered that may be involved in the regulation of transcriptional disorders and affected the survival of PAAD patients, which would provide a novel strategy for the treatment of PAAD. Dove 2021-08-03 /pmc/articles/PMC8349199/ /pubmed/34377019 http://dx.doi.org/10.2147/CMAR.S316935 Text en © 2021 Shang et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Shang, Xin Shi, Lan-Er Taule, Dina Zhu, Zhang-Zhi A Novel miRNA–mRNA Axis Involves in Regulating Transcriptional Disorders in Pancreatic Adenocarcinoma |
title | A Novel miRNA–mRNA Axis Involves in Regulating Transcriptional Disorders in Pancreatic Adenocarcinoma |
title_full | A Novel miRNA–mRNA Axis Involves in Regulating Transcriptional Disorders in Pancreatic Adenocarcinoma |
title_fullStr | A Novel miRNA–mRNA Axis Involves in Regulating Transcriptional Disorders in Pancreatic Adenocarcinoma |
title_full_unstemmed | A Novel miRNA–mRNA Axis Involves in Regulating Transcriptional Disorders in Pancreatic Adenocarcinoma |
title_short | A Novel miRNA–mRNA Axis Involves in Regulating Transcriptional Disorders in Pancreatic Adenocarcinoma |
title_sort | novel mirna–mrna axis involves in regulating transcriptional disorders in pancreatic adenocarcinoma |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349199/ https://www.ncbi.nlm.nih.gov/pubmed/34377019 http://dx.doi.org/10.2147/CMAR.S316935 |
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