Abstract 3077: LARP7: Potential novel tumor suppressor gene in gastric cancer

Abstract

Abstract Gastric cancer is one of the most deadly of all human tumors. However, little is known about events leading to this deadly disease. We previously reported that the RNA binding protein gene, La ribonucleoprotein domain family, member 7 (LARP7) was frequently subjected to genetic aberration in gastric cancers. LARP7 stabilizes the noncoding 7sk small nuclear RNA (7sk), and both LARP7 and 7sk compose 7sk snRNP that negatively regulates the positive transcription elongation factor b (P-TEFb). Hyperactive P-TEFb has been associated with hyper-proliferation and de-differentiation in various tissues. Therefore, the functional loss of LARP7 may contribute to gastric tumorigenesis. In the current study, we evaluated the involvement of LARP7 in human gastric cancer by assessing the LARP7 expression in normal and cancerous gastric tissues as well as by LARP7 knockdown in normal gastric epithelial cells. Methods: LARP7 expression was assessed by real-time quantitative RT-PCR in 30 normal and 25 cancerous gastric tissues. LARP7 knockdown was performed by the specific siRNA transient transfection in an immortalized normal human gastric epithelial cell line, HFE-145. Results: LARP7 mRNA expression was significantly decreased in gastric cancers compare to normal tissues (34.5% reduction, p<0.01). LARP7-targeting siRNA transfection in HFE-145 cells resulted in increased cell proliferation by 23% relative to the control siRNA transfection (p<0.05; measured by WST assay). We also observed a 28% decrease in 7sk quantity in LARP7-targeting siRNA transfectant relative to control siRNA transfectant (p<0.01). Conclusions: LARP7 downregulation is present in primary human gastric cancers and promotes 7sk downregulation as well as cell proliferation of normal gastric epithelial cells in vitro. Taken together, genetic aberrations that downregulate LARP7 may promote gastric tumorigenesis via p-TEFb deregulation. Further studies are warranted to explore the precise anti-tumor mechanisms of LARP7 and its potential role in the clinical care of patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3077.