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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月2日

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  • 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

摘要

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.