1,721,011 research outputs found
COMBINAZIONE DI INIBITORI DEL FATTORE HIF-1 E AGONISTI DEL RECETTORE TLR3 PER LA TERAPIA DI TUMORI SOLIDI
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MicroRNAs as new Characters in the Plot between Epigenetics and Prostate Cancer
No full textProstate cancer (PCA) still represents a leading cause of death. An increasing number of studies have documented that microRNAs (miRNAs), a subgroup of non-coding RNAs with gene regulatory functions, are differentially expressed in PCA respect to the normal tissue counterpart, suggesting their involvement in prostate carcinogenesis and dissemination. Interestingly, it has been shown that miRNAs undergo the same regulatory mechanisms than any other protein coding gene, including epigenetic regulation. In turn, miRNAs can also affect the expression of oncogenes and tumor suppressor genes by targeting effectors of the epigenetic machinery, therefore indirectly affecting the epigenetic controls on these genes. Among the genes that undergo this complex regulation, there is the androgen receptor (AR), a key therapeutic target for PCA. This review will focus on the role of epigenetically regulated and epigenetically regulating miRNAs in prostate cancer and on the fine regulation of AR expression, as mediated by this miRNA-epigenetics interaction
Beyond nitrogen metabolism: nitric oxide, cyclic-di-GMP and bacterial biofilms
No full textThe nitrogen cycle pathways are responsible for the circulation of inorganic and organic N-containing molecules in nature. Among these pathways, those involving amino acids, N-oxides and in particular nitric oxide (NO) play strategic roles in the metabolism of microorganisms in natural environments and in host-pathogen interactions. Beyond their role in the N-cycle, amino acids and NO are also signalling molecules able to influence group behaviour in microorganisms and cell-cell communication in multicellular organisms, including humans.In this mini-review, we summarize the role of these compounds in the homeostasis of the bacterial communities called biofilms, commonly found in environmental, industrial and medical settings. Biofilms are difficult to eradicate since they are highly resistant to antimicrobials and to the host immune system. We highlight the effect of amino acids such as glutamate, glutamine and arginine and of NO on the signalling pathways involved in the metabolism of 3', 5'-cyclic diguanylic acid (c-di-GMP), a master regulator of motility, attachment and group behaviour in bacteria. The study of the metabolic routes involving these N-containing compounds represents an attractive topic to identify targets for biofilm control in both natural and medical settings
A conserved scaffold with heterogeneous metal ion binding site: the multifaceted example of HD-GYP proteins
No full textThe control of the intracellular level of cyclic dinucleotides is a major strategy to transduce external signals into a cellular response, particularly in bacteria. The HD-GYP metalloproteins, a subgroup of the larger family of histidine-aspartate (HD) hydrolases, can catalyze the cleavage of the phosphodiester bond(s) of cyclic dinucleotides. The HD signature is involved in metal binding in the active site, whereas the GYP motif is likely involved in recognition and interaction with other partners. The most representative substrate of HD-GYPs is the second messenger cyclic-di-GMP (c-di-GMP), a global regulator of bacterial biofilm, motility, and virulence. Hydrolysis of c-di-GMP into the linear form pGpG or into the monomeric guanosine derivative (GMP) reprograms the cellular phenotype, usually promoting biofilm dispersion and virulence. Recent data indicate that members of HD-GYP group can also hydrolyze the bacterial cyclic diGMP-AMP (cGAMP) dinucleotide or act as possible sensors of pGpG.
The HD-GYP diversity is not limited to substrate recognition: the most striking trait is the extraordinary heterogeneity of the active sites characterized so far, showing different metals ions assisting catalysis, both in terms of their nature and number. In this review, we provide a critical overview of the structural, functional, and kinetic properties of the bacterial HD-GYP metalloproteins
SHMT1 knockdown induces apoptosis in lung cancer cells by causing uracil misincorporation
No full textReprogramming of cellular metabolism towards de novo serine production fuels the growth of cancer cells, providing essential
Q1 precursors such as amino acids and nucleotides and controlling the antioxidant and methylation capacities of the cell. The enzyme
serine hydroxymethyltransferase (SHMT) has a key role in this metabolic shift, and directs serine carbons to one-carbon units
metabolism and thymidilate synthesis. While the mitochondrial isoform of SHMT (SHMT2) has recently been identified as an
important player in the control of cell proliferation in several cancer types and as a hot target for anticancer therapies, the role of
the cytoplasmic isoform (SHMT1) in cancerogenesis is currently less defined. In this paper we show that SHMT1 is overexpressed
in tissue samples from lung cancer patients and lung cancer cell lines, suggesting that, in this widespread type of tumor, SHMT1
plays a relevant role. We show that SHMT1 knockdown in lung cancer cells leads to cell cycle arrest and, more importantly, to p53-
dependent apoptosis. Our data demonstrate that the induction of apoptosis does not depend on serine or glycine starvation, but is
because of the increased uracil accumulation during DNA replication
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