维持平衡的脂质状态以防止脂毒性在各种肿瘤中至关重要。包括结直肠癌(CRC)。胡尔,RNA结合蛋白家族成员,在许多癌症中表现出高表达,可能是因为它调节细胞增殖,迁移,入侵,和脂质代谢。然而,HuR在调节CRC脂质代谢异常中的作用尚不清楚。我们发现,HuR促进维生素D受体(VDR)的表达,以确保脂质稳态通过增加甘油三酯(TG)和总胆固醇(TC)水平在CRC,从而证实了过表达的HuR与Vdr的CDS和3'-UTR的直接结合,增强其表达。同时,HuR可通过抑制miR-124-3p间接影响VDR表达。HuR可以抑制miR-124-3p的表达,绑定到Vdr的3'-UTR,从而减少VDR表达。此外,异种移植模型表明,靶向HuR抑制VDR表达,阻断TG和TC的形成,从而减轻CRC增长。我们的发现表明HuR之间存在调节关系,miR-124-3p,和CRC中的VDR。我们建议HuR/miR-124-3p/VDR复合物通过影响CRC中的TG和TC形成来控制脂质稳态。为CRC的预防和治疗提供潜在的治疗靶点。
Maintaining a balanced lipid status to prevent lipotoxicity is of paramount importance in various tumors, including colorectal cancer (CRC). HuR, an RNA-binding protein family member, exhibits high expression in many cancers possibly because it regulates cell proliferation, migration, invasion, and lipid metabolism. However, the role of HuR in the regulation of abnormal lipid metabolism in CRC remains unknown. We found that HuR promotes vitamin D receptor (VDR) expression to ensure lipid homeostasis by increasing Triglyceride (TG) and Total Cholesterol (TC) levels in CRC, thus confirming the direct binding of an overexpressed HuR to the CDS and 3\'-UTR of Vdr, enhancing its expression. Concurrently, HuR can indirectly affect VDR expression by inhibiting miR-124-3p. HuR can suppress the expression of miR-124-3p, which binds to the 3\'-UTR of Vdr, thereby reducing VDR expression. Additionally, a xenograft model demonstrated that targeting HuR inhibits VDR expression, blocking TG and TC formation, and hence mitigating CRC growth. Our findings suggest a regulatory relationship among HuR, miR-124-3p, and VDR in CRC. We propose that the HuR/miR-124-3p/VDR complex governs lipid homeostasis by impacting TG and TC formation in CRC, offering a potential therapeutic target for CRC prevention and treatment.