Abstract
BackgroundRecent 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.ResultsWe 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.ConclusionTaken together, we concluded that RASAL1 inhibited colon cancer cell proliferation via modulating SCD1 activity through LXRα/SREBP1c pathway.
Highlights
Recent studies have confirmed that RAS protein activator like 1 (RASAL1) has an antitumor effect in many cancers, but its functional role and the molecular mechanism underlying in colon cancer has not been investigated
Since Ras as the upstream in the regulating of SREBP1c expression [15], RASAL1 as the RAS guanosine triphosphate hydrolases (GTPases)-activating protein, so we suggest whether RASAL regulate the Stearoyl-coenzyme A desaturase 1 (SCD1) activity via liver X receptor α (LXRα) and SREBP-1 pathway in colon cancer
RASAL1 is expressed at a low level in colon cancer In order to understand the role of RASAL1 during the progress of colon cancer, we first determined the expression levels of RASAL1 in 27 pairs of colon cancer tissues and adjacent normal tissues using quantitative RT-qPCR
Summary
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. Multiple factors are involved in the occurrence and development of colon cancer, including the activation of oncogenes and inactivation of tumor suppressor genes [3]. The RAS GTPase-activating protein (Ras-GAP) gene RASAL1 has been demonstrated as a tumor suppressor gene which act as a negative modulator of the RAS signaling pathway by catalyzing RAS inactivation [5]. RASAL1 expression is decreased in many tumors, including thyroid cancer, gastric cancer, prostatic cancer and bladder cancer [5,6,7,8], but its functional role in colon cancer has not been investigated. The RAS oncogene family could encode membrane-associated proteins involved in mediation of signals arising from binding of ligands to cell membrane receptors such as epidermal growth factor receptors (EGFRs) to nuclear transcription factors [9]
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