miR-210 Locus Deletion Disrupts Cellular Homeostasis; An Integrated Genetic Study

MiR-210 is widely recognized as the quintessential hypoxia-responsive miRNA and thought to fine-tune various facets of cellular homeostasis. We hereby present an integrative appraisal of phenotypic and molecular repercussions of disrupting the corresponding locus in human and mouse cells using multiple genetic strategies. Briefly, MIR210 deletion led to decreased cellular fitness and suboptimal responses to several stress types. Transcriptomic comparisons using different profiling platforms, performed independently by members of this collaboration, revealed consistent deregulation of neighboring genes, in locus-disrupted cells. Interestingly, the anticipated enrichment in 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 note of caution for studies based for genetic disruption of such loci. mRNA-seq of WT, MIR210-KO, and MIR210HG-KO HEK cells cultured under normoxic (21% O₂) or hypoxic (1% O₂) conditions for 24 hours.