Aplasia ras homolog member I is downregulated in gastric cancer and silencing its expression promotes cell growth in vitro

• Published in: Journal of gastroenterology and hepatology Vol. 27; no. 8; pp. 1395 - 1404
• Main Authors: Tang, Hai-Ling, Hu, Yi-Qun, Qin, Xing-Ping, Jazag, Amarsanaa, Yang, Hong, Yang, Yi-Xuan, Yang, Xiao-Ning, Liu, Jing-Jing, Chen, Jian-Min, Guleng, Bayasi, Ren, Jian-Lin
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Publishing Asia 01.08.2012
• Subjects: Aplasia ras homolog member I; Apoptosis; Blotting, Western; Cell Differentiation; Cell Line, Tumor; Cell Movement; Cell Proliferation; Down-Regulation; Enzyme Activation; gastric cancer; Gene Expression Regulation, Neoplastic; Gene Silencing; HEK293 Cells; Humans; Immunohistochemistry; Male; Middle Aged; Neoplasm Staging; Phosphorylation; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; rho GTP-Binding Proteins - genetics; rho GTP-Binding Proteins - metabolism; RNA Interference; RNA, Messenger - metabolism; Signal Transduction; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Transfection; tumor suppressor gene
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1111/j.1440-1746.2012.07146.x

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.