Concordant dysregulation of miR-5p and miR-3p arms of the same precursor microRNA may be a mechanism in inducing cell proliferation and tumorigenesis: a XXXX study.

@entity5 @entity4009 @entity2 @entity3373
UNASSIGNED: A precursor microRNA (miRNA) has two arms: miR-5p and miR-3p (miR-5p/-3p). Depending on the tissue or cell types, both arms can become functional. However, little is known about their coregulatory mechanisms during the tumorigenic process. Here, by using the large-scale miRNA expression profiles of five @entity5 types, we revealed that several of miR-5p/-3p arms were concordantly dysregulated in each @entity5 . To explore possible coregulatory mechanisms of concordantly dysregulated miR-5p/-3p pairs, we developed a robust computational framework and applied it to @entity2 data. The framework deciphers miR-5p/-3p coregulated protein interaction networks critical to @entity2 development. As a novel part in the method, we uniquely applied the second-order partial correlation to minimize false-positive regulations. Using 279 matched miRNA and mRNA expression profiles extracted from @entity5 and normal lung tissue samples, we identified 17 aberrantly expressed miR-5p/-3p pairs that potentially modulate the gene expression of 35 protein complexes. Functional analyses revealed that these complexes are associated with @entity5 -related biological processes, suggesting the oncogenic potential of the reported miR-5p/-3p pairs. Specifically, we revealed that the reduced expression of @entity3373 -5p/-3p pair potentially contributes to elevated expression of genes in the " @entity4009 transcription factor network" pathway, which may consequently lead to uncontrolled cell proliferation. Subsequently, the regulation of @entity3373 -5p/-3p in the @entity4009 signaling pathway was validated by a cohort of 104 matched miRNA and protein (reverse-phase protein array) expression profiles in @entity2 . In summary, our computational framework provides a novel tool to study miR-5p/-3p coregulatory mechanisms in @entity5 .
