Proteomic screening identifies PML/p53 axis as a potential treatment target of facial nerve schwannomas

作者: Hongsai Chen , Zhaoyan Wang , Hao Wu , Zhigang Wang , Lu Xue

DOI:

关键词: MutationCancer researchNucleoplasmActivator (genetics)CytoplasmPromyelocytic leukemia proteinBiologySuppressorProteomeMerlin (protein)

摘要: Facial nerve schwannomas (FNS) represents one of the more difficult treatment paradigms in neurotology. The aim this study is to investigate molecular alterations FNS, thus providing potential targets treatable tumour. We for first time suggest that deficiency merlin (the product NF2 tumour suppressor) probably key mechanisms underlying FNS tumourigenesis, although no disease-causing mutations were demonstrated samples. TMT-labeled spectrometry analysis was used identify proteome relative controls. Eighty-four significantly deregulated proteins identified, among which PML suppressor showed most increased expression. protein distributed nucleoplasm non-tumorous Schwann cells, whereas it preferentially confined cytoplasm cultures. Overexpression and p53, partner positively regulating each other trigger apoptosis, further confirmed tissues/cultures, correlated with a significant decrease proliferation cultures comparison cells. It therefore probable PML-p53 overexpression may occur as part protective cellular response signal mediated by loss accordance fact benign slow-growing. This hypothesis supported finding p53 activator nutlin-3 could exert dose-dependent inhibitory effects on via cooperative induction levels. Thus, current present target directed disease.

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