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

Proteomic screening identifies PML/p53 axis as a potential treatment target of facial nerve schwannomas.
Am J Transl Res. 2020;12(8):4237-4250
Authors: Wang Z, Chen H, Xue L, He W, Jiang L, Wang Z, Wu H
Abstract
Facial nerve schwannomas (FNS) represents one of the more difficult treatment paradigms in neurotology. The aim of this study is to investigate the molecular alterations of FNS, thus providing potential targets treatable in the tumour. We for the first time suggest that the deficiency of merlin (the product of NF2 tumour suppressor) is probably one of the key mechanisms underlying FNS tumourigenesis, although no disease-causing NF2 mutations were demonstrated in tumour samples. TMT-labeled spectrometry analysis was used to identify the proteome of FNS relative to nerve controls. Eighty-four significantly deregulated proteins were identified, among which the PML tumour suppressor showed the most significantly increased expression. The PML protein was distributed in the nucleoplasm of non-tumorous Schwann cells, whereas it was preferentially confined to the cytoplasm of FNS cultures. Overexpression of PML and p53, partner proteins positively regulating each other to trigger apoptosis, was further confirmed in FNS tissues/cultures, and this correlated with a significant decrease in the proliferation of FNS cultures in comparison to Schwann cells. It is therefore probable that PML-p53 overexpression may occur as part of protectiv...

Source: American Journal of Translational Research - September 13, 2020 Category: Research Tags: Am J Transl Res Source Type: research