MED27 promotes melanoma growth by targeting AKT/MAPK and NF-κB/iNOS signaling pathways

Cancer Letters
Ranran TangWuguo Deng

Abstract

The inhibitors of BRAF and MEK targeting MAPK signaling pathway provide a comparatively effective therapeutic strategy for melanoma caused by BRAF mutation. However, melanoma, especially metastatic melanoma, has become one of the most threatening malignancies. Thus, the identification of exact molecular mechanisms and the key components involved in such mechanisms is urgently needed in order to provide new therapeutic options for patients with melanoma. Here, we identified MED27 as a potential melanoma target and explored its role and the associated molecular mechanism involved in melanoma progression. MED27 was found to be highly expressed in melanoma cells and tumor tissues. Its silencing led to melanoma cell proliferation inhibition, cell cycle arrest and apoptosis induction accompanied by the inactivation of PI3K/AKT and MAPK/ERK signaling and the activation of Bax/Cyto-C/Caspase-dependent apoptotic pathway. In addition, silencing of MED27 led to the decrease of iNOS expression through inhibiting the activation of a serial of upstream key proteins of NF-κB signaling pathway and the translocation of p50/p65 from cytoplasm to nucleus. MED27 was also found to be able to interact with NF-κB and p300 and to be acetylated by p300...Continue Reading

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Citations

Nov 10, 2020·Cell Death and Differentiation·Yina LiaoWuguo Deng

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