{Reference Type}: Journal Article
{Title}: Review of the Different Outcomes Produced by Genetic Knock Out of the Long Non-coding microRNA-host-gene MIR22HG versus Pharmacologic Antagonism of its Intragenic microRNA product miR-22-3p.
{Author}: Thibonnier M;Ghosh S;
{Journal}: Microrna
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jun 28
暂无{DOI}: 10.2174/0122115366282339240604042154
{Abstract}: <B>BACKGROUND: </B>Publications reveal different outcomes achieved by genetically knocking out a long non-coding microRNA-host-gene (lncMIRHG) versus the administration of pharma-cologic antagomirs specifically targeting the guide strand of such intragenic microRNA. This suggests that lncMIRHGs may perform diverse functions unrelated to their role as intragenic miRNA precursors.<BR><B>OBJECTIVE: </B>This review synthesizes in silico, in vitro, and in vivo findings from our lab and others to compare the effects of knocking out the long non-coding RNA MIR22HG, which hosts miR-22, versus administering pharmacological antagomirs targeting miR-22-3p.<BR><B>METHODS: </B>In silico analyses at the gene, pathway, and network levels reveal both distinct and overlapping targets of hsa-miR-22-3p and its host gene, MIR22HG. While pharmacological an-tagomirs targeting miR-22-3p consistently improve various metabolic parameters in cell culture and animal models across multiple studies, genetic knockout of MIR22HG yields inconsistent results among different research groups.<BR><B>RESULTS: </B>Additionally, MIR22HG functions as a circulating endogenous RNA (ceRNA) or "sponge" that simultaneously modulates multiple miRNA-mRNA interactions by competing for binding to several miRNAs.<BR><B>CONCLUSIONS: </B>From a therapeutic viewpoint, genetic inactivation of a lncMIRHG and pharmaco-logic antagonism of the guide strand of its related intragenic miRNA produce different results. This should be expected as lncMIRHGs play dual roles, both as lncRNA and as a source for primary miRNA transcripts.