ABSTRACT
BACKGROUND: Recent studies have confirmed that RASAL1 has an antitumor effect in many cancers, but its functional role and the molecular mechanism underlying in colon cancer has not been investigated. RESULTS: We collected human colon cancer tissues and adjacent non-tumor tissues, human colon cancer cell lines LoVo, CaCo2, SW1116, SW480 and HCT-116, and normal colonic mucosa cell line NCM460. RT-qPCR was used to detect the RASAL1 level in the clinical tissues and cell lines. In LoVo and HCT-116, RASAL1 was artificially overexpressed. Cell viability and proliferation were measured using CCK-8 assays, and cell cycle was detected via PI staining and flow cytometry analysis. RASAL1 significantly inhibited the cell proliferation via inducing cell cycle arrest, suppressed cell cycle associated protein expression, and decreased the lipid content and inhibited the SCD1 expression. Moreover, SCD1 overexpression induced and downregulation repressed cell proliferation by causing cell cycle arrest. Additionally, luciferase reporter assays were performed to confirm the direct binding between SREBP1c, LXRα; and SCD1 promoter, we also demonstrated that RASAL1 inhibit SCD1 3'-UTR activity. RASAL1 inhibited tumor growth in xenograft nude mice models and shows inhibitory effect of SCD1 expression in vivo. CONCLUSION: Taken together, we concluded that RASAL1 inhibited colon cancer cell proliferation via modulating SCD1 activity through LXRα/SREBP1c pathway.
Subject(s)
Humans , Animals , Mice , Stearoyl-CoA Desaturase/metabolism , Colonic Neoplasms/pathology , GTPase-Activating Proteins/metabolism , Cell Proliferation/physiology , Sterol Regulatory Element Binding Protein 1/metabolism , Liver X Receptors/metabolism , Stearoyl-CoA Desaturase/genetics , Down-Regulation , GTPase-Activating Proteins/genetics , Cell Line, Tumor , Sterol Regulatory Element Binding Protein 1/genetics , Liver X Receptors/geneticsABSTRACT
Una proteína soluble (Mr=12 000) similar a FABP es parcialmente purificada a partir de citosol de hígado de rata (15 veces, considerando su afinidad por ácido oleico) por precipitación con sulfato de amonio. Durante la incubación de microsomas de hígado de rata conteniendo cantidades similares de los ácidos esteátrico y oleico, con esta proteína, hubo una disociación selectiva del ácido oleico desde la membrana microsomal. Cuando se agrega a microsomas una fracción enriquecida en esta proteína se estimula la desaturación del ácido esteárico. Este efecto es eliminado si la proteína es presaturada con ácido oleico. Se sugiere que esta proteína estimula la desaturación del ácido esteárico por un mecanismo que involucra la remoción del producto de la reacción