作为肾细胞癌的潜在治疗靶点。

as a Potential Therapeutic Target for Renal Cell Carcinoma.

机构信息

Department of Parasitology, Guangdong Medical University, 524023 Zhanjiang, Guangdong, China.

School of Medical Technology, Guangdong Medical University, 523808 Dongguan, Guangdong, China.

出版信息

Front Biosci (Landmark Ed). 2023 Sep 12;28(9):196. doi: 10.31083/j.fbl2809196.

DOI:10.31083/j.fbl2809196

PMID:37796681

Abstract

BACKGROUND

Serine hydroxymethyltransferase () is a serine-glycine-one-carbon metabolic enzyme in which and encode the cytoplasmic and mitochondrial isoenzymes, respectively. and are key players in cancer metabolic reprogramming, and thus are attractive targets for cancer therapy. However, the role of in patients with renal cell carcinoma (RCC) has not been fully elucidated. We aimed to systematically analyze the expression, gene regulatory network, prognostic value, and target prediction of and in patients with kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), and kidney renal papillary cell carcinoma (KIRP); elucidate the association between expression and RCC; and identify potential new targets for clinical RCC treatment.

METHODS

Several online databases were used for the analysis, including cBioPortal, TRRUST, GeneMANIA, GEPIA, Metascape, UALCAN, LinkedOmics, and TIMER.

RESULTS

and transcript levels were significantly down- and upregulated, respectively, in patients with KICH, KIRC, and KIRP, based on sample type, individual cancer stage, sex, and patient age. Compared to men, women with KIRC and KIRP showed significantly up- and downregulated transcript levels, respectively. However, transcript levels were significantly upregulated in the patients mentioned above. KIRC and KIRP patients with high expression had longer survival periods than those with low expression. In patients with KIRC, the findings were similar to those mentioned above. However, in KICH patients, the findings were the opposite regarding expression. versus were altered by 9% versus 3% (n = 66 KICH patients), 4% versus 4% (n = 446 KIRC patients), and 6% versus 7% (n = 280 KIRP patients). versus promoter methylation levels were significantly up- and downregulated in patients with KIRP versus KIRC and KIRP, respectively. , , and their neighboring genes (NG) formed a complex network of interactions. The molecular functions of and its NG in patients with KICH, KIRC, and KIRP, included clathrin adaptor, metalloendopeptidase, and GTPase regulator activities; lipid binding, active transmembrane transporter activity, and lipid transporter activity; and type I interferon receptor binding, integrin binding, and protein heterodimerization, respectively. Their respective Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were involved in lysosome activity, human immunodeficiency virus 1 infection, and endocytosis; coronavirus disease 2019 and neurodegeneration pathways (multiple diseases); and RIG-I-like receptor signaling pathway, cell cycle, and actin cytoskeleton regulation. The molecular functions of and its NG in patients with KICH, KIRC, and KIRP included cell adhesion molecule binding and phospholipid binding; protein domain-specific binding, enzyme inhibitor activity, and endopeptidase activity; and hormone activity, integrin binding, and protein kinase regulator activity, respectively. For patients with KIRC versus KIRP, the KEGG pathways were involved in cAMP and calcium signaling pathways versus microRNAs (MiRNAs) in cancer cells and neuroactive ligand-receptor interactions, respectively. We identified the key transcription factors of and its NG.

CONCLUSIONS

and expression levels were different in patients with RCC. and may be potential therapeutic and prognostic biomarkers in these patients. Transcription factor (MYC, STAT1, PPARG, AR, SREBF2, and SP3) and miRNA (miR-17-5P, miR-422, miR-492, miR-137, miR-30A-3P, and miR-493) regulations may be important strategies for RCC treatment.

摘要

背景

丝氨酸羟甲基转移酶（）是丝氨酸-甘氨酸一碳代谢酶，其中和分别编码细胞质和线粒体同工酶。和是癌症代谢重编程的关键参与者，因此是癌症治疗的有吸引力的靶点。然而，在肾细胞癌（RCC）患者中的作用尚未完全阐明。我们旨在系统分析、在肾嫌色细胞癌（KICH）、肾透明细胞癌（KIRC）和肾乳头状细胞癌（KIRP）患者中的表达、基因调控网络、预后价值和预测靶点；阐明与 RCC 相关的表达情况；并确定临床 RCC 治疗的潜在新靶点。

方法

使用包括 cBioPortal、TRRUST、GeneMANIA、GEPIA、Metascape、UALCAN、LinkedOmics 和 TIMER 在内的多个在线数据库进行分析。

结果

根据样本类型、个体癌症分期、性别和患者年龄，与 KICH、KIRC 和 KIRP 患者相比，和的转录水平分别显著下调和上调。与男性相比，女性 KIRC 和 KIRP 患者的和转录水平分别显著上调和下调。然而，上述患者的水平显著上调。与低表达相比，表达水平较高的 KIRC 和 KIRP 患者的生存时间更长。在 KIRC 患者中，结果与上述结果相似。然而，在 KICH 患者中，关于表达的结果则相反。与相比，在 66 例 KICH 患者（n=66 KICH 患者）中，改变了 9%，而改变了 3%；在 446 例 KIRC 患者（n=446 KIRC 患者）中，改变了 4%，而改变了 4%；在 280 例 KIRP 患者（n=280 KIRP 患者）中，改变了 6%，而改变了 7%。与 KIRP 相比，KIRC 和 KIRP 患者的和启动子甲基化水平分别显著上调和下调。、和它们的邻近基因（NG）形成了一个复杂的相互作用网络。、及其 NG 在 KICH、KIRC 和 KIRP 患者中的分子功能包括网格蛋白衔接蛋白、金属内肽酶和 GTPase 调节剂活性；脂质结合、活性跨膜转运蛋白活性和脂质转运蛋白活性；以及 I 型干扰素受体结合、整合素结合和蛋白质异源二聚化。它们各自的京都基因与基因组百科全书（KEGG）途径分别涉及溶酶体活性、人类免疫缺陷病毒 1 感染和内吞作用；冠状病毒病 2019 和神经退行性疾病途径（多种疾病）；以及 RIG-I 样受体信号通路、细胞周期和肌动蛋白细胞骨架调节。、及其 NG 在 KICH、KIRC 和 KIRP 患者中的分子功能包括细胞粘附分子结合和磷脂结合；蛋白结构域特异性结合、酶抑制剂活性和内肽酶活性；以及激素活性、整合素结合和蛋白激酶调节剂活性。对于 KIRC 与 KIRP 患者，KEGG 途径分别涉及 cAMP 和钙信号通路与癌症细胞中的 microRNAs（miRNAs）和神经活性配体-受体相互作用。我们确定了和及其 NG 的关键转录因子。

结论

在 RCC 患者中，和的表达水平不同。和可能是这些患者潜在的治疗和预后生物标志物。转录因子（MYC、STAT1、PPARG、AR、SREBF2 和 SP3）和 miRNA（miR-17-5P、miR-422、miR-492、miR-137、miR-30A-3P 和 miR-493）调节可能是 RCC 治疗的重要策略。