Mutation R273H confers p53 a stimulating effect on the IGF-1R-AKT pathway via miR-30a suppression in breast cancer.

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
Fangdong GuoLin Zhang

Abstract

p53 is the most highly mutated tumor suppressor in human malignancies. A wide array of p53 mutations has been revealed to play pivotal roles during cancer progression, which abolish anti-tumor functions of wild type p53 but also elicit tumorigenic effects by activating a diverse subset of downstream molecules. R273H mutation of p53 has been closely implicated in human cancer. Here we report miR-30a as a novel downstream target of p53 R273H mutant, which binds to the promoter region to repress miR-30a expression. Consequently, p53 R273H mutant enhances the migratory capabilities of tumor cells that are compromised by exogenous miR-30a over-expression. Our further investigation indicates that p53 R273H mutation unleashes the inhibition effect of miR-30a on IGF-1R expression, thus leading to elevated activation of IGF-1R-AKT signaling cascade in tumor cells.

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Citations

Jan 23, 2019·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Fan TangZhenfeng Duan
Apr 19, 2018·Cell Death and Differentiation·Alessandra di GennaroRoberta Maestro
Mar 1, 2020·Biomolecules·Marco CordaniMassimo Donadelli

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