Deregulation ofARID1A,CDH1,cMETandPIK3CAand target-related microRNA expression in gastric cancer

Abstract

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 GCrelated 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.

ARID1A knockdown triggers epithelial‐mesenchymal transition and carcinogenesis features of renal cells: role in renal cell carcinoma

“…2). These results were consistent with those previously reported, showing that ARID1A knockdown or deficiency or deregulation was associated with decreased apoptosis but increased cell proliferation, invasion, and migration of liver, breast, ovarian, and gastric cancer cells (29,(32)(33)(34). Regulation of ARID1A in apoptosis evasion remains unclear but may involve inhibition of Fas-mediated cell death, which was suggested by a previous study showing that suppression of ARID1A by short hairpin RNA inhibited both Fas-Ab-induced caspase-8 cleavage and mitochondrial potential reduction (35).…”

“…The correlation between EMT and survival has been recently reported in RCC patients (43). Activation of EMT process has been reported in pancreatic and gastric cancers, showing the increased mesenchymal features, decreased epithelial phenotypes, and increased migrating activity of the ARID1A ‐mutant/knockdown cells (34, 44, 45). Our results were consistent with those reported in such previous studies demonstrating that the siARID1A‐transfected MDCK cells exhibited morphologic changes and other characteristics of EMT (Fig.…”

Sulforaphane improves chemotherapy efficacy by targeting cancer stem cell-like properties via the miR-124/IL-6R/STAT3 axis

“…As a tumor suppressor, aberrant low expression of miR-124 is often detected in many tumors, such as gynecological, cerebral, and gastric tumors454647. MiR-124 was reported to perform crucial anti-cancer functions in GC4849. It also plays important roles in mediating CSCs.…”

Digital PCR identifies changes in CDH1 (E-cadherin) transcription pattern in intestinal-type gastric cancer

“…Previous evaluations obtained by qPCR method on intestinal GCs gave variable results with reports ranging from a clear decrease [11, 21] to a non-significant difference [22, 23] in CDH1 expression in cancer compared to the normal counterpart. Therefore, through the implementation of the more precise dPCR in our quantification, we were able to provide evidence on the downregulation of CDH1 expression.…”