Your browser doesn't support javascript.
loading
LARP7 is a potential tumor suppressor gene in gastric cancer.
Cheng, Yulan; Jin, Zhe; Agarwal, Rachana; Ma, Ke; Yang, Jian; Ibrahim, Soibrahim; Olaru, Alexandru V; David, Stefan; Ashktorab, Hassan; Smoot, Duane T; Duncan, Mark D; Hutcheon, David F; Abraham, John M; Meltzer, Stephen J; Mori, Yuriko.
Afiliación
  • Cheng Y; Division of Gastroenterology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Lab Invest ; 92(7): 1013-9, 2012 Jul.
Article en En | MEDLINE | ID: mdl-22488152
We previously reported frequent truncating mutations of the RNA-binding protein gene, La ribonucleoprotein domain family, member-7 (LARP7) in gastric cancers (GCs) with frequent microsatellite instability. LARP7 negatively regulates positive transcription elongation factor-b (p-TEFb) by binding to and stabilizing 7sk RNA. p-TEFb has been linked to proliferation and de-differentiation in various tissues. Therefore, we reasoned that loss of LARP7 may contribute to gastric tumorigenesis. In this study, we evaluated LARP7 mRNA expression in 18 GCs, their corresponding non-neoplastic gastric tissues (N(GC)), and 18 normal gastric tissues from healthy individuals (N(N)). We also assessed the effects of transient small interfering (siRNA)-mediated LARP7 knockdown in immortalized non-neoplastic gastric epithelial cells. LARP7 mRNA was significantly decreased in GCs (median 2.5) relative to N(N)s (median 14.9, P<0.01) as well as relative to their corresponding N(GC)s (median 8.1, P<0.01). Transfection of an siRNA directed against LARP7 (anti-LARP7 siRNA) into non-neoplastic gastric epithelial cells decreased 7sk levels by 72% relative to a control siRNA (P<0.01). Furthermore, anti-LARP7 siRNA transfection increased cell proliferation by 23% (P<0.01) and cell migration by 22% (P<0.001) relative to control siRNA transfection. Taken together, these findings suggest that LARP7 downregulation occurs early during gastric tumorigenesis and may promote gastric tumorigenesis via p-TEFb dysregulation.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ribonucleoproteínas / Neoplasias Gástricas / Genes Supresores de Tumor Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Lab Invest Año: 2012 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ribonucleoproteínas / Neoplasias Gástricas / Genes Supresores de Tumor Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Lab Invest Año: 2012 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos