Integrated Analysis of microRNA Targets Reveals New Insights into Transcriptional–Post-Transcriptional Regulatory Cross-Talk

It is becoming increasingly clear that microRNAs are key players in gene regulatory networks, modulating gene expression at post-transcriptional level. Their involvement in almost all cellular processes predicts their role in diseases, and several microRNA-based therapeutics are currently undergoing...

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Main Authors: Simona Panni, Roberto Pizzolotto
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/14/1/43
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author Simona Panni
Roberto Pizzolotto
author_facet Simona Panni
Roberto Pizzolotto
author_sort Simona Panni
collection DOAJ
description It is becoming increasingly clear that microRNAs are key players in gene regulatory networks, modulating gene expression at post-transcriptional level. Their involvement in almost all cellular processes predicts their role in diseases, and several microRNA-based therapeutics are currently undergoing clinical testing. Despite their undeniable relevance and the substantial body of literature demonstrating their role in cancer and other pathologies, the identification of functional interactions is still challenging. To address this issue, several resources have been developed to collect information from the literature, according to different criteria and reliability scores. In the present study, we have constructed a network of verified microRNA-mRNA interactions by integrating strong-evidence couples from different resources. Our analysis of the resulting network reveals that only one-fifth of the human genes exhibits experimental validated regulation by microRNAs. A very small subset of them is controlled by more than 20 microRNAs, and these hubs are highly enriched of pivotal transcription factors and regulatory proteins, strongly suggesting a complex interplay and a combinatorial effect between transcriptional and post-transcriptional gene control. Data analysis also reveals that several microRNAs control multiple targets involved in the same pathway or biological process, likely contributing to the coordinated control of the protein levels.
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spelling doaj-art-e107351862c547d489d46e9632f842402025-01-24T13:23:24ZengMDPI AGBiology2079-77372025-01-011414310.3390/biology14010043Integrated Analysis of microRNA Targets Reveals New Insights into Transcriptional–Post-Transcriptional Regulatory Cross-TalkSimona Panni0Roberto Pizzolotto1Dipartimento di Biologia Ecologia Scienze della Terra (DiBEST), Università della Calabria, 87036 Rende, CS, ItalyDipartimento di Biologia Ecologia Scienze della Terra (DiBEST), Università della Calabria, 87036 Rende, CS, ItalyIt is becoming increasingly clear that microRNAs are key players in gene regulatory networks, modulating gene expression at post-transcriptional level. Their involvement in almost all cellular processes predicts their role in diseases, and several microRNA-based therapeutics are currently undergoing clinical testing. Despite their undeniable relevance and the substantial body of literature demonstrating their role in cancer and other pathologies, the identification of functional interactions is still challenging. To address this issue, several resources have been developed to collect information from the literature, according to different criteria and reliability scores. In the present study, we have constructed a network of verified microRNA-mRNA interactions by integrating strong-evidence couples from different resources. Our analysis of the resulting network reveals that only one-fifth of the human genes exhibits experimental validated regulation by microRNAs. A very small subset of them is controlled by more than 20 microRNAs, and these hubs are highly enriched of pivotal transcription factors and regulatory proteins, strongly suggesting a complex interplay and a combinatorial effect between transcriptional and post-transcriptional gene control. Data analysis also reveals that several microRNAs control multiple targets involved in the same pathway or biological process, likely contributing to the coordinated control of the protein levels.https://www.mdpi.com/2079-7737/14/1/43microRNAbiocurationmiRNA interaction networkgene regulationtranscription factors
spellingShingle Simona Panni
Roberto Pizzolotto
Integrated Analysis of microRNA Targets Reveals New Insights into Transcriptional–Post-Transcriptional Regulatory Cross-Talk
Biology
microRNA
biocuration
miRNA interaction network
gene regulation
transcription factors
title Integrated Analysis of microRNA Targets Reveals New Insights into Transcriptional–Post-Transcriptional Regulatory Cross-Talk
title_full Integrated Analysis of microRNA Targets Reveals New Insights into Transcriptional–Post-Transcriptional Regulatory Cross-Talk
title_fullStr Integrated Analysis of microRNA Targets Reveals New Insights into Transcriptional–Post-Transcriptional Regulatory Cross-Talk
title_full_unstemmed Integrated Analysis of microRNA Targets Reveals New Insights into Transcriptional–Post-Transcriptional Regulatory Cross-Talk
title_short Integrated Analysis of microRNA Targets Reveals New Insights into Transcriptional–Post-Transcriptional Regulatory Cross-Talk
title_sort integrated analysis of microrna targets reveals new insights into transcriptional post transcriptional regulatory cross talk
topic microRNA
biocuration
miRNA interaction network
gene regulation
transcription factors
url https://www.mdpi.com/2079-7737/14/1/43
work_keys_str_mv AT simonapanni integratedanalysisofmicrornatargetsrevealsnewinsightsintotranscriptionalposttranscriptionalregulatorycrosstalk
AT robertopizzolotto integratedanalysisofmicrornatargetsrevealsnewinsightsintotranscriptionalposttranscriptionalregulatorycrosstalk