Reciprocal Regulatory Loop Between Akt and miRNA301 - Relevance for Tumor Progression

Micro-RNAs (miRs) have emerged as a new category of genes withregulatory function towards the expression of other genes, mainlyat various levels of mRNA maturation, stability and translation. Theanomalous expression of a number of miRs has recently been associatedwith different types of cancers. We have investigated the functionalinteractions between selected miRs and major pro-survival signalingpathways. We have observed that miR301 inhibition influencesPI3K-Akt pathway activity. The overexpression of Akt in MCF7 andMDAMB468 cells caused downregulation of miR301 expression.This effect was confirmed by co-transfection of miR301-modulatorsin the presence of Akt. Cells overexpressing miR301-inhibitor andAkt, exhibited an increased migration and an enhanced proliferation.Experimental findings also validated that the PI3K, PTEN and FoxF2could be the regulatory targets for miR301. Furthermore, Akt expressionin conjunction with miR301-inhibitor increased nuclear accumulationof PTEN, thus preventing it from downregulating the PI3K-signalling. Insummary, our findings highlight the significance of miR301 inhibition onPI3K-Akt pathway-mediated cellular functions. As a result, we envisionthat it opens new paths for the development of new anti-cancer agentsfavorably with the potential of targeting the PI3K-Akt pathway.

کلیدواژه ها:

miRNA301 ، PI3K-Akt pathway