Aplasia ras homolog member I is downregulated in gastric cancer and silencing its expression promotes cell growth in vitro
Aplasia ras homolog member I is downregulated in gastric cancer and silencing its expression promotes cell growth in vitro
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Aplasia ras 同源物成员 I 在胃癌中下调，沉默其表达可促进体外细胞生长
DOI：
10.1111/j.1440-1746.2012.07146.x
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发表时间：
2012-08-01
影响因子：
4.1
通讯作者：
Ren, Jian-Lin
中科院分区：
文献类型：
--
作者：
Tang, Hai-Ling;Hu, Yi-Qun;Ren, Jian-Lin
背景与目的：再生障碍性贫血ras基因同源物I（ARHI）是一种具有母源性印记的抑癌基因. ARHI蛋白广泛表达于多种人体组织中，但在多种肿瘤中表达减少或缺失，在体外研究中具有抑癌作用。在这项研究中，我们研究了胃癌中ARHI的表达水平，以探讨ARHI的功能和信号通路，可能在胃癌的发展。研究方法：分别采用半定量PCR、免疫印迹和免疫组化方法检测胃癌组织、癌旁组织和胃癌细胞系中ARHI mRNA和蛋白的表达水平。结果如下：结果显示，胃癌组织和胃癌细胞株中ARHI基因的mRNA和蛋白表达水平均显著低于相应的正常对照组（P < 0.05）。ARHI蛋白表达水平与胃癌患者的年龄、性别、肿瘤部位、肿瘤大小及转移无关。ARHI蛋白表达水平与肿瘤分化程度、肿瘤淋巴结转移分期相关（P < 0.05）。此外，甲基噻唑基四唑和Transwell分析和流式细胞仪分析的结果显示，在分化良好的胃癌MKN-28细胞系中，细胞增殖，迁移和抗凋亡能力增加，该细胞系具有稳定沉默的ARHI蛋白表达。结论：我们的数据表明，ARHI在人胃癌中表达下调，它可能是一个新的肿瘤抑制靶点，用于胃癌治疗。
Background and Aim: Aplasia ras homolog member I (ARHI) is a maternally imprinted tumor suppressor gene. ARHI protein is widely expressed in many types of human tissues; however, its expression is frequently reduced or absent in various tumors and plays a tumor suppressor role for in vitro study. In this study, we investigated the expression level of ARHI in gastric cancer in order to investigate the function of ARHI and signaling pathways that might be linked during gastric cancer development. Methods: ARHI mRNA and protein expression levels were analyzed in primary gastric cancer tissues, adjacent noncancerous gastric tissues and gastric cancer cell lines using semi-quantitative polymerase chain reaction, western blotting and immunohistochemistry, respectively. Results: Our results showed that both mRNA and protein expression levels of the ARHI gene were significantly downregulated (P < 0.05) in gastric cancer tissues and cell lines compared to the corresponding normal control groups. The protein expression level of ARHI was not associated with age, gender, location of tumor, tumor size or metastasis in patients with gastric cancer. However, a significant correlation between the level of ARHI protein expression and the degree of tumor differentiation and Tumor-Node-Metastasis stage was observed (P < 0.05). Furthermore, results of the methyl thiazolyl tetrazolium and Transwell assays and flow cytometric analysis showed increased cell proliferation, migration and anti-apoptotic capacities in the well-differentiated gastric cancer MKN-28 cell line, which has stably silenced ARHI protein expression. Conclusion: Our data indicate that ARHI expression is downregulated in human gastric cancer and it may be a novel tumor suppressive target for gastric cancer therapy.