Deregulation of ARID1A, CDH1, cMET and PIK3CA and target-related microRNA expression in gastric cancer.
Deregulation of ARID1A, CDH1, cMET and PIK3CA and target-related microRNA expression in gastric cancer.
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DOI：
10.18632/oncotarget.4775
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发表时间：
2015-09-29
期刊：
影响因子：
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通讯作者：
Cervantes A
中科院分区：
文献类型：
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作者：
Ibarrola-Villava M;Llorca-Cardeñosa MJ;Tarazona N;Mongort C;Fleitas T;Perez-Fidalgo JA;Roselló S;Navarro S;Ribas G;Cervantes A
遗传学和表观遗传学改变在胃癌发病机制中起重要作用。磷脂酰肌醇-3-激酶信号通路的畸变已被充分描述。然而，已经描述了新兴基因，例如染色质重塑基因ARID 1A。我们的目的是确定4个GC相关基因ARID 1A、CDH 1、cMET和PIK 3CA以及14个靶相关microRNA（miRNAs）的表达水平。我们采用实时定量逆转录PCR技术比较了66例胃癌和癌旁正常黏膜组织中mRNA和miRNA的表达水平。此外，通过免疫组织化学（IHC）评估ARID 1A、cMET和PIK 3CA蛋白水平。最后，还评估了基因和miRNAs与临床特征和结果的相关性。在78.0%（P = 2.20 × 10−5）和73.8%（P = 1.00 × 10−3）的肿瘤中分别发现cMET和PIK 3CA mRNA表达增加。此外，IHC显示cMET和PIK 3CA表达分别在63.6%和87.8%的肿瘤中呈阳性。6个miRNAs在配对样本中有显著差异表达，发现5个上调的[miR-223- 3 p（P = 1.65 × 10−6），miR-19a-3p（P = 1.23 × 10−4），miR-128-3p（P = 3.49 × 10−4）、miR-130 b-3 p（P = 1.00 × 10−3）和miR-34 a-5 p（P = 4.00 × 10−3）]和1个下调[miR-124- 3 p（P = 0.03）]。我们的数据表明，cMET，PIK 3CA和靶点相关的miRNA在GC中发挥重要作用，并可能作为潜在的治疗靶点。
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.