6533b851fe1ef96bd12a8f5d

RESEARCH PRODUCT

Deregulation of ARID1A, CDH1, cMET and PIK3CA and target-related microRNA expression in gastric cancer.

Cristina MongortMaider Ibarrola-villavaSamuel NavarroAndrés CervantesMarta J. Llorca-cardeñosaT. FleitasGloria RibasAlejandro Pérez-fidalgoNoelia TarazonaSusana Roselló

subject

MaleARID1AClass I Phosphatidylinositol 3-KinasesReal-Time Polymerase Chain ReactionCDH1Epigenesis GeneticPhosphatidylinositol 3-KinasesAntigens CDStomach NeoplasmsGene expressionmicroRNAmedicineBiomarkers TumorHumansRNA MessengerAgedbiologyReverse Transcriptase Polymerase Chain ReactionGene Expression Profilinggastric cancerCancerNuclear ProteinsbiomarkersMiddle AgedProto-Oncogene Proteins c-metmedicine.diseaseCadherinsMolecular biologyImmunohistochemistryChromatinGene expression profilingReverse transcription polymerase chain reactionDNA-Binding ProteinsGene Expression Regulation NeoplasticMicroRNAsReal-time polymerase chain reactionmicrorna expressionOncologyGastric Mucosabiology.proteingene expressionFemaleTranscription FactorsResearch Paper

description

Genetic and epigenetic alterations play an important role in gastric cancer (GC) pathogenesis. Aberrations of the phosphatidylinositol-3-kinase signaling pathway are well described. However, emerging genes have been described such as, the chromatin remodeling gene ARID1A. Our aim was to determine the expression levels of four GC-related genes, ARID1A, CDH1, cMET and PIK3CA, and 14 target-related microRNAs (miRNAs). We compared mRNA and miRNA expression levels among 66 gastric tumor and normal adjacent mucosa samples using quantitative real-time reverse transcription PCR. Moreover, ARID1A, cMET and PIK3CA protein levels were assessed by immunohistochemistry (IHC). Finally, gene and miRNAs associations with clinical characteristics and outcome were also evaluated. An increased cMET and PIK3CA mRNA expression was found in 78.0% (P = 2.20 × 10-5) and 73.8% (P = 1.00 × 10-3) of the tumors, respectively. Moreover, IHC revealed that cMET and PIK3CA expression was positive in 63.6% and 87.8% of the tumors, respectively. Six miRNAs had significantly different expression between paired-samples, finding five up-regulated [miR-223-3p (P = 1.65 × 10-6), miR-19a-3p (P = 1.23 × 10-4), miR-128-3p (P = 3.49 × 10-4), miR-130b-3p (P = 1.00 × 10-3) and miR-34a-5p (P = 4.00 × 10-3)] and one down-regulated [miR-124-3p (P = 0.03)]. Our data suggest that cMET, PIK3CA and target-related miRNAs play an important role in GC and may serve as potential targets for therapy.

yearjournalcountryeditionlanguage
2015-07-27Oncotarget
10.18632/oncotarget.4775https://pubmed.ncbi.nlm.nih.gov/26334097