The mutation of TP53 gene affects half of all human cancers, resulting in impairment of the regulation of several cellular functions, including cell cycle progression and cell death in response to genotoxic stress. In the recent years additional p53-mediated tumour suppression mechanisms have been described, questioning the contribution of its canonical pathway for tumour suppression. These include regulation of alternative cell death modalities (i.e. ferroptosis), cell metabolism and the emerging role in RNA stability. Here we briefly summarize our knowledge on p53 "canonical DNA damage response" and discuss the most relevant recent findings describing potential mechanistic explanation of p53-mediated tumour suppression.

BACKGROUND: Growing evidence has demonstrated that long non-coding RNAs (lncRNAs) can function as modulators in the development of triple-negative breast cancer (TNBC). However, the function of lncRNA small nucleolar RNA host gene 8 (SNHG8) in TNBC remains unclear. Therefore, our study aimed at investigating the role of SNHG8 in the proliferation and migration of TNBC cells. METHODS: SNHG8 expression was evaluated using RT-qPCR assay. Cell proliferation and migration were assessed by EdU, colony formation and Transwell assays. The levels of proteins related to EMT process were examined by western blot assay. The interaction among SNHG8, miR-335-5p and pygopus family PHD finger 2 (PYGO2) was detected by RIP assay, RNA pull down assay and luciferase reporter assay. RESULTS: SNHG8 expression was significantly up-regulated in TNBC cells. SNHG8 silencing obviously inhibited TNBC cell proliferation, migration and EMT process. Moreover, SNHG8 acted as a sponge to sequester miR-335-5p in TNBC cells. Besides, PYGO2 was proven as a target gene of miR-335-5p, and SNHG8 promoted TNBC cell proliferation, migration and EMT process through regulating miR-335-5p and PYGO2. CONCLUSIONS: Totally, our study indicated that SNHG8 promoted TNBC cell proliferation and migration by regulating the miR-335-5p/PYGO2 axis.

Lifestyle is one of the most powerful instruments shaping mankind; the lifestyle includes many aspects of interactions with the environment, from nourishment and education to physical activity and quality of sleep. All these factors taken in complex affect neuroplasticity and define brain performance and cognitive longevity. In particular, physical exercise, exposure to enriched environment and dieting act through complex modifications of microglial cells, which change their phenotype and modulate their functional activity thus translating lifestyle events into remodelling of brain homoeostasis and reshaping neural networks ultimately enhancing neuroprotection and cognitive longevity.

Most inactivating mutations in TP53 gene generates neomorphic forms of p53 proteins that experimental evidence and clinical observations suggest to exert gain-of-function effects. While massive effort has been deployed in the dissection of wild type p53 transcriptional programme, p53 mutant pro-tumorigenic gene network is still largely elusive. To help dissecting the molecular basis of p53 mutant GOF, we performed an analysis of a fully annotated genomic and transcriptomic human pancreatic adenocarcinoma to select candidate players of p53 mutant network on the basis their differential expression between p53 mutant and p53 wild-type cohorts and their prognostic value. We identified NUAK2 and RCan2 whose p53 mutant GOF-dependent regulation was further validated in pancreatic cancer cellular model. Our data demonstrated that p53R270H can physically bind RCan2 gene locus in regulatory regions corresponding to the chromatin permissive areas where known binding partners of p53 mutant, such as p63 and Srebp, bind. Overall, starting from clinically relevant data and progressing into experimental validation, our work suggests NUAK2 and RCan2 as novel candidate players of the p53 mutant pro-tumorigenic network whose prognostic and therapeutic interest might attract future studies.