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Choline-induced SLC5A7 impairs colorectal cancer growth by stabilizing p53 protein
Cancer Letters ( IF 9.1 ) Pub Date : 2021-09-22 , DOI: 10.1016/j.canlet.2021.09.027
Yuan Yin 1 , Zhiyuan Jiang 1 , Jiamei Fu 2 , Yang Li 3 , Chao Fang 1 , Xiaonan Yin 1 , Ye Chen 4 , Na Chen 2 , Junshu Li 2 , Yanhong Ji 2 , Xiaolan Su 2 , Meng Qiu 4 , Wei Huang 5 , Bo Zhang 1 , Hongxin Deng 2 , Lei Dai 2
Affiliation  

The members of the solute carrier (SLC) superfamily are vital membrane transporters in human cells. In the present study, we determine the expression and function of SLC5 family members in colorectal cancer (CRC). Expression analysis based on The Cancer Genome Atlas database and potential clinical relation analysis based on the Oncomine database indicate that SLC5A7 is downregulated and is predicted to correlate with the staging, and prognosis response of CRC. Additional results demonstrate that SLC5A7 is downregulated and correlates with good prognosis in patients with CRC. Ectopic expression of SLC5A7 either by overexpression, or uptake of choline efficiently inhibits CRC growth. Examination of the molecular mechanism reveals that SLC5A7 promotes p53 protein expression by directly interacting with and modifying p53 and disrupting the interaction between p53 and MDM2 in wild type p53 CRC cells. Our findings establish the clear correlation between SLC5A7 and tumour growth, providing a novel potential therapeutic target for CRC.



中文翻译:

胆碱诱导的 SLC5A7 通过稳定 p53 蛋白来损害结直肠癌的生长

溶质载体 (SLC) 超家族的成员是人体细胞中重要的膜转运蛋白。在本研究中,我们确定了 SLC5 家族成员在结直肠癌 (CRC) 中的表达和功能。基于癌症基因组图谱数据库的表达分析和基于 Oncomine 数据库的潜在临床关系分析表明,SLC5A7 被下调,预计与 CRC 的分期和预后反应相关。其他结果表明,SLC5A7 被下调并与 CRC 患者的良好预后相关。SLC5A7 通过过度表达或胆碱摄取的异位表达可有效抑制 CRC 生长。分子机制的检查表明,SLC5A7 通过直接与 p53 相互作用和修饰 p53 并破坏野生型 p53 CRC 细胞中 p53 和 MDM2 之间的相互作用来促进 p53 蛋白表达。我们的研究结果建立了 SLC5A7 与肿瘤生长之间的明确相关性,为 CRC 提供了一个新的潜在治疗靶点。

更新日期:2021-11-02
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