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. 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. Taken together, we concluded that RASAL1 inhibited colon cancer cell proliferation via modulating SCD1 activity through LXRα/SREBP1c pathway.

中文翻译：

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RASAL1诱导下调SCD1，从而通过LXRα/ SREBP1c途径抑制结肠癌细胞的增殖

最近的研究证实，RASAL1在许多癌症中均具有抗肿瘤作用，但尚未研究其功能作用和结肠癌中潜在的分子机制。我们收集了人类结肠癌组织和邻近的非肿瘤组织，人类结肠癌细胞系LoVo，CaCo2，SW1116，SW480和HCT-116，以及正常结肠黏膜细胞系NCM460。RT-qPCR用于检测临床组织和细胞系中的RASAL1水平。在LoVo和HCT-116中，RASAL1被人为过表达。使用CCK-8测定法测量细胞活力和增殖，并通过PI染色和流式细胞仪分析检测细胞周期。RASAL1通过诱导细胞周期停滞，抑制细胞周期相关蛋白表达来显着抑制细胞增殖，降低脂质含量并抑制SCD1表达。此外，SCD1的过表达诱导和下调通过引起细胞周期停滞来抑制细胞增殖。另外，进行荧光素酶报告基因测定以证实SREBP1c，LXRα和SCD1启动子之间的直接结合，我们还证明了RASAL1抑制SCD1 3'-UTR活性。RASAL1抑制异种移植裸鼠模型中的肿瘤生长，并在体内显示出SCD1表达的抑制作用。两者合计，我们得出结论，RASAL1通过通过LXRα/ SREBP1c途径调节SCD1活性来抑制结肠癌细胞的增殖。LXRα和SCD1启动子，我们还证明RASAL1抑制SCD1 3'-UTR活性。RASAL1抑制异种移植裸鼠模型中的肿瘤生长，并在体内显示出SCD1表达的抑制作用。两者合计，我们得出结论，RASAL1通过通过LXRα/ SREBP1c途径调节SCD1活性来抑制结肠癌细胞的增殖。LXRα和SCD1启动子，我们还证明RASAL1抑制SCD1 3'-UTR活性。RASAL1抑制异种移植裸鼠模型中的肿瘤生长，并在体内显示出SCD1表达的抑制作用。两者合计，我们得出结论，RASAL1通过通过LXRα/ SREBP1c途径调节SCD1活性来抑制结肠癌细胞的增殖。