微陣列通路分析表明，在子宮內膜癌中，有絲分裂原激活的蛋白激酶/細胞外信號調節激酶和胰島素生長因子1信號通路被小干擾RNA抑制

2017年3月，南京醫科大學附屬上海總醫院婦產科；上海交通大學附屬上海總醫院婦產科(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老師研究團隊在《Biochemical and Biophysical Research Communications》上發表論文：

“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”

“微陣列通路分析表明，在子宮內膜癌中，有絲分裂原激活的蛋白激酶/細胞外信號調節激酶和胰島素生長因子1信號通路被小干擾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：

在子宮內膜癌(EC)中經常觀察到編碼富含at的相互作用結構域1A (ARID1A)的基因突變，但與遺傳變化相關的分子機制仍未完全了解。本研究旨在闡明ARID1A突變對信號通路的影響。通過Sanger測序驗證EC HEC-1-A細胞系中存在錯義、同義和無義雜合ARID1A突變。將突變的ARID1A小干擾RNA轉染到HEC-1-A細胞中。生化芯片分析顯示，arid1a缺失突變的HEC-1-A細胞中有13條上調通路，17條下調通路，14條顯著影響疾病狀態和功能，662個上游基因和512個下游基因，其中絲裂原活化蛋白激酶/細胞外信號調節激酶和胰島素樣生長因子-1 (IGF1)信號通路下調最多。叉頭盒蛋白O1通路上調，IGF1受體、胰島素受體底物1和磷脂酰肌醇-4,5-二磷酸3-激酶催化亞基b通路下調。腫瘤發生、腫瘤細胞有絲分裂和腫瘤細胞死亡均顯著上調疾病狀態和功能，而細胞增殖和腫瘤生長均顯著下調。本研究結果提示ARID1A可能是預防EC進展的潛在預后和治療性分子藥物靶點。

該論文中，人子宮內膜癌HEC-1-A細胞的體外培養是使用Ausbian特級胎牛血清完成的。欲了解或購買Ausbian特級胎牛血清可以聯系北京締一生物400-166-8600.