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| 1 | Interplay between post-translational cyclooxygenase-2 modifications and the metabolic and proteomic profile in a colorectal cancer cohort显示文摘BACKGROUND Colorectal cancer(CRC) is the second most common cause of cancer death worldwide. It is broadly described that cyclooxygenase-2(COX-2) is mainly overexpressed in CRC but less is known regarding post-translational modifications of this enzyme that may regulate its activity, intracellular localization and stability. Since metabolic and proteomic profile analysis is essential for cancer prognosis and diagnosis, our hypothesis is that the analysis of correlations between these specific parameters and COX-2 state in tumors of a high number of CRC patients could be useful for the understanding of the basis of this cancer in humans.AIM To analyze COX-2 regulation in colorectal cancer and to perform a detailed analysis of their metabolic and proteomic profile.METHODS Biopsies from both healthy and pathological colorectal tissues were taken under informed consent from patients during standard colonoscopy procedure in the University Hospital of Bellvitge(Barcelona, Spain) and Germans Trias i Pujol University Hospital(Campus Can Ruti)(Barcelona, Spain). Western blot analysis was used to determine COX-2 levels. Deglycosylation assays were performed in both cells and tumor samples incubating each sample with peptide N-glycosidase F(PNGase F). Prostaglandin E2(PGE2) levels were determined using a specific ELISA. 1 H high resolution magic angle spinning(HRMAS) analysis was performed using a Bruker AVIII 500 MHz spectrometer and proteomic analysis was performed in a nano-liquid chromatography-tandem mass spectrometer(nano LC-MS/MS) using a QExactive HF orbitrap MS.RESULTS Our data show that COX-2 has a differential expression profile in tumor tissue of CRC patients vs the adjacent non-tumor area, which correspond to a glycosylated and less active state of the protein. This fact was associated to a lesser PGE2 production in tumors. These results were corroborated in vitro performing deglycosylation assays in HT29 cell line where COX-2 protein profile was modified after PNGase F incubation, showing higher PGE2 levels. Moreover,HRMAS analysis indicated that tumor tissue has altered metabolic features vs non-tumor counterparts, presenting increased levels of certain metabolites such as taurine and phosphocholine and lower levels of lactate. In proteomic experiments, we detected an enlarged number of proteins in tumors that are mainly implicated in basic biological functions like mitochondrial activity,DNA/RNA processing, vesicular trafficking, metabolism, cytoskeleton and splicing.CONCLUSION In our colorectal cancer cohort, tumor tissue presents a differential COX-2 expression pattern with lower enzymatic activity that can be related to an altered metabolic and proteomic profile. | Patricia Prieto Rafael I Jaén Daniel Calle María Gómez-Serrano Estefanía Nú?ez María Fernández-Velasco Paloma Martín-Sanz Sergio Alonso Jesús Vázquez Sebastián Cerdán Miguel ángel Peinado Lisardo Boscá | 2019 | World Journal of Gastroenterology2019，25，4： | 4 |
| 2 | Nested PCR improves detection of infectious hematopoietic necrosis virus in cells coinfected with infectious pancreatic necrosis virus显示文摘 | Marta Alonso Sylvia Rodr??guez Sara I Pérez Prieto | 1999 | Journal of Virological Methods1999，，1： | 2 |
| 3 | A new role of diacylglycerol kinase α on the secretion of lethal exosomes bearing FasL ligand during activation-induced cell death of T lymphocytes显示文摘 | Alonso R Mazzeo C Merida I | 2007 | Biochimie2007，89，： | 1 |
| 4 | Transcription regulatory sequences and mRNA expression levels in the coro- navirus transmissible gastroenteritis virus 显示文摘 | Alonso S Izeta A Sola I | 2002 | Journal of Virology2002，76，3： | 1 |
| 5 | Bile duct reconstruction using 3-dimensional collagen tubes 显示文摘 | Pérez Alonso AJ Del Olmo Rivas C Machado Romero I | 2013 | Cir Esp2013，91，9： | 1 |
| 6 | High-risk cervical epithelial neoplasia grade 1 treated by loop electrosurgical excision:follow-up and value of HPV testing显示文摘 | ALONSO I TORNéA1 | 2007 | Am J Obstet Gynecol2007，197，4： | 1 |
| 7 | Nucleotide sequence of the genomic RNA of pepper mild mottle virus a resistance-breaking tobamovirus in pepper显示文摘 | ALONSO E GARCIA-LUQUE I DELA C A | 1991 | J Gen Virol1991，72，： | 1 |
| 8 | Alzheimer' s disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disas- sembles microtubules 显示文摘 | Alonso AC Grundke-Iqbal I Iqbal K | 1996 | Nat Med1996，2，7： | 1 |
| 9 | J Am Chem Soc显示文摘 | Castro R Cuadrado I Alonso B | 1997 | 119:5 7601997，119，： | 1 |
| 10 | ,Hardy inequalities and some critical elliptic and parabolic prob- lems显示文摘 | Garcia AzoreroJ Peral Alonso I | 1998 | Diff Equs1998，144，： | 1 |
| 11 | Multiplicity of solutions for elliptic problems with critical exponent or with a nonsymmetric term显示文摘 | AZORERO J P G ALONSO I P | 1991 | Tram Amer Math Soc1991，323，2： | 1 |
| 12 | Synthesis of titanium oxide parti- cles in supercritical CO2: Effect of operational variables in the character- istics of the final product显示文摘 | Alonso E Montequi I Lucas S | 2007 | The Journal of Supercritcal Fluids2007，39，3： | 1 |
| 13 | On-Line Solid-Phase Chelation for the Determination of Six Metals in Sea Water by Inductively Coupled Plasma Mass Spectrometry 显示文摘 | SANCH EZ T RUJILLO I VEREDA ALONSO E SILES CORDERO M T | 2010 | Journal of Analyti- cal Atomic Spectrometry2010，25，： | 1 |
| 14 | Baseline of butyltin pollution in coastal sediments within the Basque Country (northern Spain), in 2007-2008显示文摘 | Rodriguez J G~ Solaun O Larreta J Segarra M J B Franco J Alonso J I G Sariego C Valencia V Borja A | 2010 | Marine Pollution Bulletin2010，60，1： | 1 |
| 15 | Galloping instabilities of two-dimensional triangular cross-section bodies 显示文摘 | Alonso G Meseguer J P6rez-Grande I | 2005 | Experiments in Fluids2005，38，6： | 1 |
| 16 | Metal-mediated reductive hydrodehalogenation of organic halides 显示文摘 | Alonso F Beletskaya I P Yus M | 2002 | Chemical Reviews2002，102，11： | 1 |
| 17 | Alzheimer's disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules显示文摘 | Alonso A C Grundke-Iqbal I Iqbal K | 1996 | Nat Med1996，2，7： | 1 |
| 18 | Improvement of tribologi- eal properties by ion implantation 显示文摘 | Onate J I Alonso F Garcia A | 1998 | Thin Solid Films1998，317，12： | 1 |
| 19 | Coronavirus reverse genet- ics and development of vectors for gene expression 显示文摘 | Enjuanes L Sola I Alonso S | 2005 | Curr Top Microbiol Immunol2005，287，： | 1 |
| 20 | Depth of brain fissures in normal fetuses by prenatal ultrasound between 19 and 30 weeks of gestation显示文摘 | Alonso I Borenstein M Grant G | 2010 | Ultrasound Obstet Gynecol2010，36，： | 1 |
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