微阵列通路分析表明，在子宫内膜癌中，有丝分裂原激活的蛋白激酶/细胞外信号调节激酶和胰岛素生长因子1信号通路被小干扰RNA抑制

2017年3月，南京医科大学附属上海总医院妇产科；上海交通大学附属上海总医院妇产科(Department of Obstetrics and Gynecology, Shanghai General Hospital of Nanjing Medical University；Department of Obstetrics and Gynecology, Shanghai General Hospital of Shanghai Jiaotong University, Shanghai 200080, P.R. China) XIAOWEI XI老师研究团队在《Biochemical and Biophysical Research Communications》上发表论文：

“Microarray pathway analysis indicated that mitogen-activated protein kinase/extracellular signal-regulated kinase and insulin growth factor 1 signaling pathways were inhibited by small interfering RNA against AT-rich interactive domain 1A in endometrial cancer”

“微阵列通路分析表明，在子宫内膜癌中，有丝分裂原激活的蛋白激酶/细胞外信号调节激酶和胰岛素生长因子1信号通路被小干扰RNA抑制”

Abstract：

Mutations in the gene encoding AT-rich interactive domain 1A (ARID1A) are frequently observed in endometrial cancer (EC) but the molecular mechanisms linking the genetic changes remain to be fully understood. The present study aimed to elucidate the influence of ARID1A mutations on signaling pathways. Missense, synonymous and nonsense heterozygous ARID1A mutations in the EC HEC-1-A cell line were verified by Sanger sequencing. Mutated ARID1A small interfering RNA was transfected into HEC-1-A cells. Biochemical microarray analysis revealed 13 upregulated pathways, 17 downregulated pathways, 14 significantly affected disease states and functions, 662 upstream and 512 downstream genes in mutated ARID1A-depleted HEC-1-A cells, among which the mitogen-activated protein kinase/extracellular signal-regulated kinase and insulin-like growth factor-1 (IGF1) signaling pathways were the 2 most downregulated pathways. Furthermore, the forkhead box protein O1 pathway was upregulated, while the IGF1 receptor, insulin receptor substrate 1 and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit b pathways were downregulated. Carcinoma tumorigenesis, tumor cell mitosis and tumor cell death were significantly upregulated disease states and functions, while cell proliferation and tumor growth were significantly downregulated. The results of the present study suggested that ARID1A may be a potential prognostic and therapeutic molecular drug target for the prevention of EC progression.

摘要：

在子宫内膜癌(EC)中经常观察到编码富含at的相互作用结构域1A (ARID1A)的基因突变，但与遗传变化相关的分子机制仍未完全了解。本研究旨在阐明ARID1A突变对信号通路的影响。通过Sanger测序验证EC HEC-1-A细胞系中存在错义、同义和无义杂合ARID1A突变。将突变的ARID1A小干扰RNA转染到HEC-1-A细胞中。生化芯片分析显示，arid1a缺失突变的HEC-1-A细胞中有13条上调通路，17条下调通路，14条显著影响疾病状态和功能，662个上游基因和512个下游基因，其中丝裂原活化蛋白激酶/细胞外信号调节激酶和胰岛素样生长因子-1 (IGF1)信号通路下调最多。叉头盒蛋白O1通路上调，IGF1受体、胰岛素受体底物1和磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基b通路下调。肿瘤发生、肿瘤细胞有丝分裂和肿瘤细胞死亡均显著上调疾病状态和功能，而细胞增殖和肿瘤生长均显著下调。本研究结果提示ARID1A可能是预防EC进展的潜在预后和治疗性分子药物靶点。

该论文中，人子宫内膜癌HEC-1-A细胞的体外培养是使用Ausbian特级胎牛血清完成的。欲了解或购买Ausbian特级胎牛血清可以联系北京缔一生物400-166-8600.