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MicroRNA function can be reversed by altering target gene expression levels.


ABSTRACT: Paradoxically, many microRNAs appear to exhibit entirely opposite functions when placed in different contexts. For example, miR-125b has been shown to be pro-apoptotic in some studies, but anti-apoptotic in others. To investigate this phenomenon, we combine computational modeling with experimental approaches to examine how the function of miR-125b in apoptosis varies with respect to the expression levels of its pro-apoptotic and anti-apoptotic targets. In doing so, we elucidate a general trend that miR-125b is more pro-apoptotic when its anti-apoptotic targets are overexpressed, whereas it is more anti-apoptotic when its pro-apoptotic targets are overexpressed. We show that it is possible to completely reverse miR-125b's function in apoptosis by modifying the expression levels of its target genes. Furthermore, miR-125b's function may also be altered by the presence of anticancer drugs. These results suggest that the function of a microRNA can vary substantially and is dependent on its target gene expression levels.

SUBMITTER: Svoronos AA 

PROVIDER: S-EPMC8560630 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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MicroRNA function can be reversed by altering target gene expression levels.

Svoronos Alexander A AA   Campbell Stuart G SG   Engelman Donald M DM  

iScience 20211002 10


Paradoxically, many microRNAs appear to exhibit entirely opposite functions when placed in different contexts. For example, miR-125b has been shown to be pro-apoptotic in some studies, but anti-apoptotic in others. To investigate this phenomenon, we combine computational modeling with experimental approaches to examine how the function of miR-125b in apoptosis varies with respect to the expression levels of its pro-apoptotic and anti-apoptotic targets. In doing so, we elucidate a general trend t  ...[more]

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