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The HMGA2-IGF2BP2 Pathway Maintains Controls Mutated N-Ras Levels in Rhabdomyosarcoma

Li, Zhizhong and Glass, David and Zhang, Yunyu (2013) The HMGA2-IGF2BP2 Pathway Maintains Controls Mutated N-Ras Levels in Rhabdomyosarcoma. Cancer Research.

Abstract

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children. In an In an effort towards to searching novel targets againstprofile mechanistic changes that might induce RMS, High-Mobility Group A2 (HMGA2) is was identified as a crucial factor that is highly expressed in RMS cells and maintains RMS cellular proliferation and survival. HMGA2 level iss are inversely correlated with myoblast differentiation. Overexpression of HMGA2 promotes myoblast growth and blocks terminal differentiation. In contrast, targeting HMGA2 expression by shRNAs resulted in decreased RMS proliferation, increased apoptosis and led to cell cycle arrest. Importantly, inducible HMGA2 shRNAs demonstrated that it this gene is indispensable for tumor maintenance in vivo. Mechanistically, HMGA2 regulates IGF2BP2, which is crucial for maintaining the mRNA stability and protein levels of NRAS and many other genes involved in, which is frequently mutated in RMS and critical for inducing the Rhabdomyosarcoma phenotype. cancer growth.

Item Type: Article
Date Deposited: 26 Apr 2016 23:46
Last Modified: 26 Apr 2016 23:46
URI: https://oak.novartis.com/id/eprint/8207

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