SLC12A8 upregulation promotes colorectal cancer progression and chemoresistance.

IF 1.5 4区 医学 Q4 ONCOLOGY Translational cancer research Pub Date : 2024-07-31 Epub Date: 2024-07-24 DOI:10.21037/tcr-24-87
Zhe Sun, Zhiyan Nie, Yao Xu, Yingshun Cui, Wenjian Ma, Tongcun Zhang
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Abstract

Background: Colorectal cancer (CRC), a prevalent gastrointestinal malignant disease, causes substantial morbidity and mortality. Identification of novel prognostic biomarkers and therapeutic targets is critically needed to improve patient outcomes. Although solute carrier family 12 member 8 (SLC12A8) has high expression in various tumors and affects tumor progression, its role in CRC remains unclear. The aim of this study was to investigate the functions of SLC12A8 in CRC.

Methods: SLC12A8 expression and its association with clinical significance in CRC patients were explored via multiple public databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), The Human Protein Atlas (HPA), The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN), and Kaplan-Meier plotter. The effects of SLC12A8 on the CRC cell apoptosis, epithelial-mesenchymal transition (EMT), reactive oxygen species (ROS) production, and sensitivity to oxaliplatin were verified by in vitro experiments.

Results: SLC12A8 expression was upregulated in CRC tissues compared with normal colorectal tissues. Furthermore, high expression of SLC12A8 was associated with poorer prognosis in CRC patients. Pathway enrichment analyses revealed SLC12A8 involvement in oxidative stress and transforming growth factor-beta (TGF-β) signaling. Experiments in CRC cells showed that SLC12A8 upregulation promoted apoptosis resistance, EMT, and inhibited ROS production. Moreover, SLC12A8 knockdown enhanced the sensitivity of CRC cells to oxaliplatin chemotherapy.

Conclusions: Our integrative analyses identify SLC12A8 as a candidate biomarker for CRC progression. Targeting SLC12A8 may improve patient responses to oxaliplatin-based treatment regimens.

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SLC12A8 上调会促进结直肠癌的进展和化疗耐药性。
背景:结直肠癌(CRC)是一种常见的胃肠道恶性疾病,会导致严重的发病率和死亡率。为改善患者预后,亟需鉴定新的预后生物标志物和治疗靶点。虽然溶质运载家族 12 成员 8(SLC12A8)在多种肿瘤中高表达并影响肿瘤的进展,但它在 CRC 中的作用仍不清楚。本研究旨在探讨 SLC12A8 在 CRC 中的功能:方法:通过多个公共数据库,包括癌症基因组图谱(TCGA)、基因型-组织表达(GTEx)、人类蛋白质图谱(HPA)、阿拉巴马大学伯明翰分校CANcer数据分析门户网站(UALCAN)和Kaplan-Meier绘图仪,探讨SLC12A8在CRC患者中的表达及其与临床意义的关联。体外实验验证了SLC12A8对CRC细胞凋亡、上皮-间质转化(EMT)、活性氧(ROS)产生以及奥沙利铂敏感性的影响:结果:与正常结直肠组织相比,SLC12A8在CRC组织中表达上调。此外,SLC12A8的高表达与CRC患者较差的预后有关。通路富集分析显示,SLC12A8 参与了氧化应激和转化生长因子-β(TGF-β)信号转导。在 CRC 细胞中进行的实验表明,SLC12A8 上调可促进细胞凋亡抵抗、EMT 和抑制 ROS 的产生。此外,敲除 SLC12A8 还能增强 CRC 细胞对奥沙利铂化疗的敏感性:结论:我们的综合分析确定了 SLC12A8 是 CRC 进展的候选生物标记物。靶向 SLC12A8 可能会改善患者对基于奥沙利铂的治疗方案的反应。
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来源期刊
CiteScore
2.10
自引率
0.00%
发文量
252
期刊介绍: Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.
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