RESUMO
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.
Assuntos
Humanos , Animais , Camundongos , Estearoil-CoA Dessaturase/metabolismo , Neoplasias do Colo/patologia , Proteínas Ativadoras de GTPase/metabolismo , Proliferação de Células/fisiologia , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Receptores X do Fígado/metabolismo , Estearoil-CoA Dessaturase/genética , Regulação para Baixo , Proteínas Ativadoras de GTPase/genética , Linhagem Celular Tumoral , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Receptores X do Fígado/genéticaRESUMO
Background There is little information on the effects of diets containing high α-linolenic acid (C18:3n-3) on liver lipid composition and lipogenic gene expressions. In this study fourteen goats (Capra aegagrus hircus) were fed either a flaxseed oil (FSO) supplemented diet containing high α-linolenic acid or a control diet without added flaxseed oil (CON) for 100-d to evaluate the effects on liver lipid composition and the gene expression of peroxisome proliferator-activated receptors (PPAR-α) and stearoyl-CoA-desaturase (SCD) in the liver. Results An increase in the levels of C18:3n-3 and C20:5n-3, C22:5n-3, C22:6n-3 was observed in the liver of FSO-treated goats. There was a significant (P < 0.05) up-regulation of PPAR-α gene expression and downregulation of SCD gene in the liver of goats fed the high α-linolenic acid diet. Conclusions In conclusion, genes associated with the control of fatty acid (FA) conversion (SCD and PPAR) were affected by the α-linolenic acid supplementation in the goat diet. It is suggested that PPAR-α is the key messenger responsible for the translation of nutritional stimuli into changes in hepatic gene expression.