高表达SLC17A9和KCNH1作为透明细胞肾细胞癌的潜在预后生物标志物和治疗靶点

IF 3.3 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Zongpan Ke, Zhiwang Tang, Deyun Shen, Yixun Liu, Yawei Shu, Xiangyu Mu, Zexuan Li, Ping Xiang, Bing Zhong, Xuechun Hu, Ruoyun Tan, Jun Xiao
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引用次数: 0

摘要

背景:囊泡核苷酸转运体溶质载体家族17成员9 (SLC17A9)最近被认为是一个重要的致癌途径调节剂,其表达水平升高与透明细胞肾细胞癌(ccRCC)的侵袭性密切相关。全面了解SLC17A9及其相关蛋白标记物的作用,为推进靶向治疗干预提供了巨大的潜力。方法:我们的研究从全面的生物信息学分析开始,以确定与ccRCC潜在相关的差异表达基因。利用癌症基因组图谱(TCGA)数据库,我们预测了这些癌症相关基因的临床相关性,并通过多种实验方法验证了它们的表达谱。通过功能分析来评估这些基因对肾癌细胞系的影响。此外,我们生成了过表达癌基因的细胞系,并通过RNA测序确定了下游靶点,随后对它们的相互作用进行了机制探索。最后,随后使用生物信息学工具评估这些基因在ccRCC患者中的诊断和预后意义。结果:生物信息学分析显示,SLC17A9在ccRCC中是一个高表达的癌基因,可作为一个强有力的预后标志物。实验验证表明,SLC17A9促进ccRCC细胞生长、增殖和迁移。基于慢病毒的实验显示,钾电压门控通道亚家族H成员1 (KCNH1)是SLC17A9调控的下游靶点(p < 0.05)。数据库分析进一步证实了KCNH1在ccRCC中的致癌作用,对患者生存具有重要意义。值得注意的是,SLC17A9和KCNH1共同驱动肾癌的发生和进展。SLC17A9和KCNH1的高表达与较差的预后相关(p < 0.001),而较低的表达水平与ccRCC患者的良好预后相关。这些发现强调了SLC17A9和KCNH1是ccRCC的关键生物标志物和潜在治疗靶点。结论:SLC17A9和KCNH1是ccRCC的关键预后生物标志物,SLC17A9通过KCNH1调控推动肿瘤进展。它们的表达上调预示着不良的临床结果,而表达水平的降低与生存率的提高相关,这突出了它们作为治疗靶点的双重作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Co-Highly Expressed SLC17A9 and KCNH1 as Potential Prognostic Biomarkers and Therapeutic Targets in Clear Cell Renal Cell Carcinoma.

Background: The vesicular nucleotide transporter Solute Carrier Family 17 Member 9 (SLC17A9) has recently been recognized as a significant modulator of oncogenic pathways, with its elevated expression levels being closely linked to the aggressiveness of clear cell renal cell carcinoma (ccRCC). A comprehensive understanding of the role of SLC17A9 and its associated protein markers presents substantial potential for the advancement of targeted therapeutic interventions.

Methods: Our study commenced with a comprehensive bioinformatics analysis to identify differentially expressed genes potentially associated with ccRCC. Leveraging The Cancer Genome Atlas (TCGA) database, we predicted the clinical relevance of these cancer-associated genes and validated their expression profiles through multiple experimental methodologies. Functional assays were conducted to assess the impact of these genes on renal cancer cell lines. Additionally, we generated cell lines overexpressing oncogenes and identified downstream targets through RNA sequencing, followed by mechanistic exploration of their interactions. Finally, bioinformatics tools were subsequently employed to assess the diagnostic and prognostic significance of these genes in patients with ccRCC.

Results: The bioinformatics analysis revealed SLC17A9 as a highly expressed oncogene in ccRCC, serving as a robust prognostic marker. Experimental validation demonstrated that SLC17A9 promotes ccRCC cell growth, proliferation, and migration. Lentivirus-based experiments revealed Potassium Voltage-Gated Channel Subfamily H Member 1 (KCNH1) as a downstream target regulated by SLC17A9 (p < 0.05). Database analysis further confirmed KCNH1's oncogenic role in ccRCC, with significant implications for patient survival. Notably, SLC17A9 and KCNH1 collaboratively drive the initiation and progression of renal cancer. Elevated expression of SLC17A9 and KCNH1 correlates with poorer prognosis (p < 0.001), whereas lower expression levels are associated with favorable outcomes in ccRCC patients. These findings highlight SLC17A9 and KCNH1 as critical biomarkers and potential therapeutic targets in ccRCC.

Conclusion: SLC17A9 and KCNH1 serve as critical prognostic biomarkers in ccRCC, with SLC17A9 driving tumor progression through KCNH1 regulation. Their upregulated expression predicts poor clinical outcomes, while reduced levels correlate with improved survival, highlighting their dual role as therapeutic targets.

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