Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Institute of Life Science, and Department of Genetics and Developmental Biology, Medical School of Southeast University, Nanjing 210009, PR China.
Oncol Rep. 2012 Oct;28(4):1475-81. doi: 10.3892/or.2012.1920. Epub 2012 Jul 19.
RAS protein activator like 1 (RASAL1) is a member of the RAS GTPase-activating protein (GAP) family, and it is an important molecule in the regulation of RAS activation. In the present study, we investigated the role of RASAL1 in gastric carcinogenesis. Decreased expression pattern of RASAL1 in gastric cancer tissues and cell lines was found in protein and RNA levels, although there was no statistically significant relationship between RASAL1 and clinicopathological features. Restored expression of RASAL1 induced by DNA methylation inhibitor 5-aza-2'-deoxycytidine (5'-AZA) and HDAC inhibitor trichostatin A (TSA) implied that RASAL1 expression is regulated by epigenetic mechanisms. The biological role of RASAL1 in gastric carcinogenesis was determined by in vitro tumorigenicity assays. Overexpression of RASAL1 showed suppression of cell proliferation due to cell apoptosis. Subsequently, enforced expression of RASAL1 repressed significantly the gastric cancer cell transformation ability. These findings demonstrated that decreased RASAL1 expression is a characteristic of gastric cancer and regulated by epigenetic mechanisms. RASAL1 may be a functional tumor suppressor involved in gastric cancer. This study provides novel insights into the biological role of RASAL1 in gastric carcinogenesis.
RAS 蛋白激活样 1（RASAL1）是 RAS GTP 酶激活蛋白（GAP）家族的一员，是调节 RAS 激活的重要分子。在本研究中，我们研究了 RASAL1 在胃癌发生中的作用。在蛋白质和 RNA 水平上均发现胃癌组织和细胞系中 RASAL1 的表达下调，但 RASAL1 与临床病理特征之间无统计学显著相关性。DNA 甲基化抑制剂 5-氮杂-2'-脱氧胞苷（5'-AZA）和组蛋白去乙酰化酶抑制剂曲古抑菌素 A（TSA）恢复 RASAL1 的表达表明 RASAL1 的表达受表观遗传机制调控。通过体外致瘤性测定确定了 RASAL1 在胃癌发生中的生物学作用。RASAL1 的过表达由于细胞凋亡导致细胞增殖受到抑制。随后，强制表达 RASAL1 显著抑制了胃癌细胞的转化能力。这些发现表明，RASAL1 表达下调是胃癌的特征，并受表观遗传机制调控。RASAL1 可能是一种参与胃癌的功能性肿瘤抑制因子。本研究为 RASAL1 在胃癌发生中的生物学作用提供了新的见解。
