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Rewired functional regulatory networks among miRNA isoforms (isomiRs) from let-7 and miR-10 gene families in cancer.

Abstract：

:Classical microRNA (miRNA) has been so far believed as a single sequence, but it indeed contains multiple miRNA isoforms (isomiR) with various sequences and expression patterns. It is not clear whether these diverse isomiRs have potential relationships and whether they contribute to miRNA:mRNA interactions. Here, we aimed to reveal the potential evolutionary and functional relationships of multiple isomiRs based on let-7 and miR-10 gene families that are prone to clustering together on chromosomes. Multiple isomiRs within gene families showed similar functions to their canonical miRNAs, indicating selection of the predominant sequence. IsomiRs containing novel seed regions showed increased/decreased biological function depending on whether they had more/less specific target mRNAs than their annotated seed. Few gene ontology(GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were shared among the target genes of the annotated seeds and the novel seeds. Various let-7 isomiRs with novel seed regions may cause opposing drug responses despite the fact that they are generated from the same miRNA locus and have highly similar sequences. IsomiRs, especially the dominant isomiRs with shifted seeds, may disturb the coding-non-coding RNA regulatory network. These findings provide insight into the multiple isomiRs and isomiR-mediated control of gene expression in the pathogenesis of cancer.

journal_name

Comput Struct Biotechnol J

journal_title

Computational and structural biotechnology journal

authors

Liang T,Han L,Guo L

doi

10.1016/j.csbj.2020.05.001

subject

Has Abstract

pub_date

2020-05-13 00:00:00

pages

1238-1248

issn

2001-0370

pii

S2001-0370(20)30264-6

journal_volume

18

pub_type

杂志文章

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