miR-210 locus deletion disrupts cellular homeostasis: an integrated genetic study

Abstract MiR-210 is widely recognized as the quintessential hypoxia-responsive miRNA and is thought to fine-tune various facets of cellular homeostasis. We hereby present an integrative appraisal of the phenotypic and molecular repercussions of disrupting the corresponding locus in human and mouse c...

Full description

Saved in:
Bibliographic Details
Main Authors: Mihai Bogdan Preda, Evelyn Gabriela Nastase-Rusu, Carmen Alexandra Neculachi, Xiaoling Zhong, Christine Voellenkle, Nathalie M. Mazure, Ovidiu Balacescu, Cristina Ivan, Xiao-Wei Zheng, Mihaela Gherghiceanu, Kevin Lebrigand, Maya Simionescu, Fabio Martelli, Bernard Mari, Sergiu-Bogdan Catrina, Alexandrina Burlacu, Mircea Ivan
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-025-07572-8
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849402887435714560
author Mihai Bogdan Preda
Evelyn Gabriela Nastase-Rusu
Carmen Alexandra Neculachi
Xiaoling Zhong
Christine Voellenkle
Nathalie M. Mazure
Ovidiu Balacescu
Cristina Ivan
Xiao-Wei Zheng
Mihaela Gherghiceanu
Kevin Lebrigand
Maya Simionescu
Fabio Martelli
Bernard Mari
Sergiu-Bogdan Catrina
Alexandrina Burlacu
Mircea Ivan
author_facet Mihai Bogdan Preda
Evelyn Gabriela Nastase-Rusu
Carmen Alexandra Neculachi
Xiaoling Zhong
Christine Voellenkle
Nathalie M. Mazure
Ovidiu Balacescu
Cristina Ivan
Xiao-Wei Zheng
Mihaela Gherghiceanu
Kevin Lebrigand
Maya Simionescu
Fabio Martelli
Bernard Mari
Sergiu-Bogdan Catrina
Alexandrina Burlacu
Mircea Ivan
author_sort Mihai Bogdan Preda
collection DOAJ
description Abstract MiR-210 is widely recognized as the quintessential hypoxia-responsive miRNA and is thought to fine-tune various facets of cellular homeostasis. We hereby present an integrative appraisal of the phenotypic and molecular repercussions of disrupting the corresponding locus in human and mouse cells using multiple genetic strategies. In brief, MIR210 deletion led to decreased cellular fitness and suboptimal responses to several stress types. Transcriptomic comparisons via different profiling platforms, performed independently by members of this collaboration, revealed consistent deregulation of neighboring genes, in locus-disrupted cells. Interestingly, the anticipated enrichment of miR-210 targets failed to materialize in unbiased analyses. Our results point to the biological significance of unrecognized regulatory elements that overlap miRNA genes and should serve as a note of caution for studies based on the genetic disruption of such loci.
format Article
id doaj-art-34f55d28c44d4e05be4f00bc637f0850
institution Kabale University
issn 2045-2322
language English
publishDate 2025-07-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj-art-34f55d28c44d4e05be4f00bc637f08502025-08-20T03:37:24ZengNature PortfolioScientific Reports2045-23222025-07-0115111210.1038/s41598-025-07572-8miR-210 locus deletion disrupts cellular homeostasis: an integrated genetic studyMihai Bogdan Preda0Evelyn Gabriela Nastase-Rusu1Carmen Alexandra Neculachi2Xiaoling Zhong3Christine Voellenkle4Nathalie M. Mazure5Ovidiu Balacescu6Cristina Ivan7Xiao-Wei Zheng8Mihaela Gherghiceanu9Kevin Lebrigand10Maya Simionescu11Fabio Martelli12Bernard Mari13Sergiu-Bogdan Catrina14Alexandrina Burlacu15Mircea Ivan16Department of Stem Cell Biology, Institute of Cellular Biology and Pathology “Nicolae Simionescu”Department of Stem Cell Biology, Institute of Cellular Biology and Pathology “Nicolae Simionescu”Department of Stem Cell Biology, Institute of Cellular Biology and Pathology “Nicolae Simionescu”Department of Medicine, Indiana University School of MedicineDepartment of Stem Cell Biology, Institute of Cellular Biology and Pathology “Nicolae Simionescu”INSERM U1065, C3M, Université Côte d’AzurDepartment of Genetics, Genomics and Experimental Pathology, The Oncology Institute “Prof. Dr. Ion Chiricuta”Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer CenterDepartment of Molecular Medicine and Surgery, Karolinska InstitutetVictor Babeș National Institute of PathologyCNRS UMR7275 Inserm 1323, IPMC, FHU- OncoAge, IHU RespiERA, Sophia Antipolis, Université Côte d’AzurDepartment of Stem Cell Biology, Institute of Cellular Biology and Pathology “Nicolae Simionescu”Department of Stem Cell Biology, Institute of Cellular Biology and Pathology “Nicolae Simionescu”CNRS UMR7275 Inserm 1323, IPMC, FHU- OncoAge, IHU RespiERA, Sophia Antipolis, Université Côte d’AzurDepartment of Molecular Medicine and Surgery, Karolinska InstitutetDepartment of Stem Cell Biology, Institute of Cellular Biology and Pathology “Nicolae Simionescu”Department of Medicine, Indiana University School of MedicineAbstract MiR-210 is widely recognized as the quintessential hypoxia-responsive miRNA and is thought to fine-tune various facets of cellular homeostasis. We hereby present an integrative appraisal of the phenotypic and molecular repercussions of disrupting the corresponding locus in human and mouse cells using multiple genetic strategies. In brief, MIR210 deletion led to decreased cellular fitness and suboptimal responses to several stress types. Transcriptomic comparisons via different profiling platforms, performed independently by members of this collaboration, revealed consistent deregulation of neighboring genes, in locus-disrupted cells. Interestingly, the anticipated enrichment of miR-210 targets failed to materialize in unbiased analyses. Our results point to the biological significance of unrecognized regulatory elements that overlap miRNA genes and should serve as a note of caution for studies based on the genetic disruption of such loci.https://doi.org/10.1038/s41598-025-07572-8Gene editing technologiesGenomic neighborhoodHypoxiamiR-210Targets
spellingShingle Mihai Bogdan Preda
Evelyn Gabriela Nastase-Rusu
Carmen Alexandra Neculachi
Xiaoling Zhong
Christine Voellenkle
Nathalie M. Mazure
Ovidiu Balacescu
Cristina Ivan
Xiao-Wei Zheng
Mihaela Gherghiceanu
Kevin Lebrigand
Maya Simionescu
Fabio Martelli
Bernard Mari
Sergiu-Bogdan Catrina
Alexandrina Burlacu
Mircea Ivan
miR-210 locus deletion disrupts cellular homeostasis: an integrated genetic study
Scientific Reports
Gene editing technologies
Genomic neighborhood
Hypoxia
miR-210
Targets
title miR-210 locus deletion disrupts cellular homeostasis: an integrated genetic study
title_full miR-210 locus deletion disrupts cellular homeostasis: an integrated genetic study
title_fullStr miR-210 locus deletion disrupts cellular homeostasis: an integrated genetic study
title_full_unstemmed miR-210 locus deletion disrupts cellular homeostasis: an integrated genetic study
title_short miR-210 locus deletion disrupts cellular homeostasis: an integrated genetic study
title_sort mir 210 locus deletion disrupts cellular homeostasis an integrated genetic study
topic Gene editing technologies
Genomic neighborhood
Hypoxia
miR-210
Targets
url https://doi.org/10.1038/s41598-025-07572-8
work_keys_str_mv AT mihaibogdanpreda mir210locusdeletiondisruptscellularhomeostasisanintegratedgeneticstudy
AT evelyngabrielanastaserusu mir210locusdeletiondisruptscellularhomeostasisanintegratedgeneticstudy
AT carmenalexandraneculachi mir210locusdeletiondisruptscellularhomeostasisanintegratedgeneticstudy
AT xiaolingzhong mir210locusdeletiondisruptscellularhomeostasisanintegratedgeneticstudy
AT christinevoellenkle mir210locusdeletiondisruptscellularhomeostasisanintegratedgeneticstudy
AT nathaliemmazure mir210locusdeletiondisruptscellularhomeostasisanintegratedgeneticstudy
AT ovidiubalacescu mir210locusdeletiondisruptscellularhomeostasisanintegratedgeneticstudy
AT cristinaivan mir210locusdeletiondisruptscellularhomeostasisanintegratedgeneticstudy
AT xiaoweizheng mir210locusdeletiondisruptscellularhomeostasisanintegratedgeneticstudy
AT mihaelagherghiceanu mir210locusdeletiondisruptscellularhomeostasisanintegratedgeneticstudy
AT kevinlebrigand mir210locusdeletiondisruptscellularhomeostasisanintegratedgeneticstudy
AT mayasimionescu mir210locusdeletiondisruptscellularhomeostasisanintegratedgeneticstudy
AT fabiomartelli mir210locusdeletiondisruptscellularhomeostasisanintegratedgeneticstudy
AT bernardmari mir210locusdeletiondisruptscellularhomeostasisanintegratedgeneticstudy
AT sergiubogdancatrina mir210locusdeletiondisruptscellularhomeostasisanintegratedgeneticstudy
AT alexandrinaburlacu mir210locusdeletiondisruptscellularhomeostasisanintegratedgeneticstudy
AT mirceaivan mir210locusdeletiondisruptscellularhomeostasisanintegratedgeneticstudy