Affiliation:
1. AptamiR Therapeutics, Inc., USA
2. Pennington Biomedical Research Center, Department of Computational Biology,
Duke-NUS Medical School, Singapore
Abstract
Background:
Publications reveal different outcomes achieved by genetically knocking
out a long non-coding microRNA-host-gene (lncMIRHG) versus the administration of pharmacologic
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.
Objective:
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.
Methods:
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 antagomirs
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.
Results:
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.
Conclusions:
From a therapeutic viewpoint, genetic inactivation of a lncMIRHG and pharmacologic
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.
Funder
Louisiana Clinical and Translational Science Center
Publisher
Bentham Science Publishers Ltd.