Xing Pu, Hao Hao, Chen Jiangbo, Qiao Xiaowen, Song Tongkun, Yang Xinying, Weng Kai, Hou Yifan, Chen Jie, Wang Zaozao, Di Jiabo, Jiang Beihai, Xing Jiadi, Su Xiangqian
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, No.52 Fucheng Road, Haidian District, Beijing, 100142, China.
Peking University Health Science Center, Beijing, 100191, China.
Cancer Cell Int. 2024 Jun 18;24(1):213. doi: 10.1186/s12935-024-03403-4.
Increasing evidence suggests that DXS253E is critical for cancer development and progression, but the function and potential mechanism of DXS253E in colorectal cancer (CRC) remain largely unknown. In this study, we evaluated the clinical significance and explored the underlying mechanism of DXS253E in CRC.
DXS253E expression in cancer tissues was investigated using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The Kaplan-Meier plot was used to assess the prognosis of DXS253E. The cBioPortal, MethSurv, and Tumor Immune Estimation Resource (TIMER) databases were employed to analyze the mutation profile, methylation, and immune infiltration associated with DXS253E. The biological functions of DXS253E in CRC cells were determined by CCK-8 assay, plate cloning assay, Transwell assay, flow cytometry, lactate assay, western blot, and qRT-PCR.
DXS253E was upregulated in CRC tissues and high DXS253E expression levels were correlated with poor survival in CRC patients. Our bioinformatics analyses showed that high DXS253E gene methylation levels were associated with the favorable prognosis of CRC patients. Furthermore, DXS253E levels were linked to the expression levels of several immunomodulatory genes and an abundance of immune cells. Mechanistically, the overexpression of DXS253E enhanced proliferation, migration, invasion, and the aerobic glycolysis of CRC cells through the AKT/mTOR pathway.
We demonstrated that DXS253E functions as a potential role in CRC progression and may serve as an indicator of outcomes and a therapeutic target for regulating the AKT/mTOR pathway in CRC.
越来越多的证据表明，DXS253E对癌症的发生和发展至关重要，但DXS253E在结直肠癌（CRC）中的功能和潜在机制仍不清楚。在本研究中，我们评估了DXS253E在CRC中的临床意义，并探讨了其潜在机制。
使用癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）研究癌组织中DXS253E的表达。采用Kaplan-Meier曲线评估DXS253E的预后。利用cBioPortal、MethSurv和肿瘤免疫评估资源（TIMER）数据库分析与DXS253E相关的突变谱、甲基化和免疫浸润情况。通过CCK-8测定、平板克隆测定、Transwell测定、流式细胞术、乳酸测定、蛋白质印迹和qRT-PCR确定DXS253E在CRC细胞中的生物学功能。
DXS253E在CRC组织中上调，DXS253E高表达水平与CRC患者的不良生存相关。我们的生物信息学分析表明，DXS253E基因高甲基化水平与CRC患者的良好预后相关。此外，DXS253E水平与几种免疫调节基因的表达水平和大量免疫细胞有关。机制上，DXS253E的过表达通过AKT/mTOR途径增强了CRC细胞的增殖、迁移、侵袭和有氧糖酵解。
我们证明DXS253E在CRC进展中发挥潜在作用，可能作为预后指标和调节CRC中AKT/mTOR途径的治疗靶点。
