Overexpression of p300 correlates with poor prognosis in patients with cutaneous squamous cell carcinoma.

BACKGROUND: It has been suggested that the p300 transcriptional coactivator participates in the regulation of a wide range of cell biological processes, and mutations in p300 have been identified in various cancers. OBJECTIVES: To investigate p300 expression in cutaneous squamous cell carcinoma (cSCC) tissues and its effect on the outcome of patients with cSCC. METHODS: Immunohistochemistry (IHC) was performed on a tissue microarray to investigate p300 expression levels in cSCC tissues. Receiver operating characteristic (ROC) curve analysis, Kaplan-Meier plots and a Cox proportional hazards regression model were used to analyse the data. RESULTS: Based on the ROC curves, we defined the cut-off score for high p300 expression as > 55% of tumour cells positively stained. High expression of p300 was observed in 86 of 165 (52·1%) of the cSCC samples and six of 30 (20%) of the adjacent normal skin tissue samples (P < 0·001). High expression of p300 was positively correlated with lymph node metastasis (P = 0·006) and advanced clinical stage (P < 0·001). In univariate survival analysis, high expression of p300 was correlated with poor patient outcomes in terms of recurrence-free survival (P = 0·006) and overall survival (P < 0·001). Moreover, p300 expression was evaluated as an independent prognostic factor in a multivariate analysis (P = 0·004). CONCLUSIONS: Our results indicate that high p300 expression is associated with aggressive features of cSCC and suggest that p300 expression, as examined by IHC, will be a promising biomarker for predicting clinical outcomes in patients with cSCC.

Amino-Nogo-A antagonizes reactive oxygen species generation and protects immature primary cortical neurons from oxidative toxicity.

Nogo-A is originally identified as an inhibitor of axon regeneration from the CNS myelin. Nogo-A is mainly expressed by oligodendrocytes, and also by some neuronal subpopulations, particularly in the developing nervous system. Although extensive studies have uncovered regulatory roles of Nogo-A in neurite outgrowth inhibition, precursor migration, neuronal homeostasis, plasticity and neurodegeneration, its cell-autonomous functions in neurons are largely uncharacterized. Here, we show that HIV-1 trans-activating-mediated amino-Nogo-A protein transduction into cultured primary cortical neurons achieves an almost complete neuroprotection against oxidative stress induced by exogenous hydrogen peroxide (H(2)O(2)). Endogenously expressed neuronal Nogo-A is significantly downregulated upon H(2)O(2) treatment. Furthermore, knockdown of Nogo-A results in more susceptibility to acute oxidative insults and markedly increases neuronal death. Interacting with peroxiredoxin 2 (Prdx2), amino-Nogo-A reduces reactive oxygen species (ROS) generation and extracellular signal-regulated kinase phosphorylation to exert neuroprotective effects. Structure-function mapping experiments reveal that, out of NiG-Δ20, a novel region comprising residues 290-562 of amino-Nogo-A is indispensable for preventing oxidative neuronal death. Moreover, mutagenesis analysis confirms that cysteine residues 424, 464 and 559 are involved in the inhibition of ROS generation and neuroprotective role of amino-Nogo-A. Our data suggest that neuronal Nogo-A might play a cell-autonomous role in improving neuronal survival against oxidative insult through interacting with Prdx2 and scavenging of ROS.