Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Departments of Oncology, Biochemistry and Molecular Biology, Cumming School of Medicine, Calgary, AB T2N 4N1, Canada.
Int J Mol Sci. 2023 Feb 21;24(5):4260. doi: 10.3390/ijms24054260.
Glycyl-tRNA synthetase (GARS) is a potential oncogene associated with poor overall survival in various cancers. However, its role in prostate cancer (PCa) has not been investigated. Protein expression of GARS was investigated in benign, incidental, advanced, and castrate-resistant PCa (CRPC) patient samples. We also investigated the role of GARS in vitro and validated GARS clinical outcomes and its underlying mechanism, utilizing The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA PRAD) database. Our data revealed a significant association between GARS protein expression and Gleason groups. Knockdown of in PC3 cell lines attenuated cell migration and invasion and resulted in early apoptosis signs and cellular arrest in S phase. Bioinformatically, higher expression was observed in TCGA PRAD cohort, and there was significant association with higher Gleason groups, pathological stage, and lymph nodes metastasis. High expression was also significantly correlated with high-risk genomic aberrations such as , , , , mutations, and , , and gene fusions. Gene Set Enrichment Analysis (GSEA) of through the TCGA PRAD database provided evidence for upregulation of biological processes such as cellular proliferation. Our findings support the oncogenic role of GARS involved in cellular proliferation and poor clinical outcome and provide further evidence for its use as a potential biomarker in PCa.
甘氨酰-tRNA 合成酶（GARS）是一种与多种癌症患者总体生存率差相关的潜在致癌基因。然而，其在前列腺癌（PCa）中的作用尚未得到研究。我们研究了良性、偶发、晚期和去势抵抗性前列腺癌（CRPC）患者样本中 GARS 的蛋白表达情况。我们还利用癌症基因组图谱前列腺腺癌（TCGA PRAD）数据库研究了 GARS 在体外的作用及其潜在机制，并验证了 GARS 的临床结果及其潜在机制。我们的数据显示，GARS 蛋白表达与 Gleason 分组之间存在显著相关性。在 PC3 细胞系中敲低 GARS 可减弱细胞迁移和侵袭，并导致早期凋亡迹象和 S 期细胞停滞。从生物信息学角度来看，在 TCGA PRAD 队列中观察到更高的 表达水平，并且与更高的 Gleason 分组、病理分期和淋巴结转移显著相关。高 表达水平也与高风险基因组异常显著相关，如 、 、 、 突变，以及 、 和 基因融合。通过 TCGA PRAD 数据库进行的 基因集富集分析（GSEA）提供了证据，表明细胞增殖等生物学过程的上调。我们的研究结果支持 GARS 的致癌作用涉及细胞增殖和不良临床结局，并为其作为前列腺癌潜在生物标志物的用途提供了进一步证据。
