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YARS as an oncogenic protein that promotes gastric cancer progression through activating PI3K-Akt signaling.

YARS 是一种致癌蛋白,通过激活 PI3K-Akt 信号促进胃癌进展。

  • 影响因子:3.23
  • DOI:10.1007/s00432-019-03115-7
  • 作者列表:"Zhang C","Lin X","Zhao Q","Wang Y","Jiang F","Ji C","Li Y","Gao J","Li J","Shen L
  • 发表时间:2020-02-01
Abstract

PURPOSE:Members of the aaRS (aminoacyl-tRNA synthetase) family are proteins controlling the aminoacylation process, in which YARS (tyrosyl-tRNA synthetase) catalyzes the binding of tyrosine to its cognate tRNA and plays an important role in basic biosynthesis. Several studies have demonstrated the association between YARS mutation and certain developmental abnormalities/diseases, yet YARS's linkage with cancer remains uncategorized. In this study, by combining in silico, in vitro, and in vivo studies, we explored the expressions and functions of YARS in gastric cancer (GC). METHODS:We evaluated YARS's distribution in tumor and paired normal tissues/specimens of GC by referring to large cohort online datasets and patient-derived tissue specimens. YARS-related changes were assessed by phenotypical/molecular experiments and RNA-sequencing analysis in GC cell lines harboring YARS knockdown or overexpression. RESULTS:Both the transcript and protein levels of YARS were evidently higher in gastric cancer tissues than in paired normal tissues. YARS knockdown induced repressed proliferation and invasiveness, as well as enhanced apoptosis in GC cell lines, while abnormally upregulating YARS expression promoted gastric cancer growth in vivo. We inferred based on RNA-sequencing that YARS modulates multiple cancerous signaling pathways and proved through cellular experiments that YARS promoted GC progression, as well as homologous recombination by activating PI3K-Akt signaling. CONCLUSIONS:By revealing the existence of a YARS-PI3K-Akt signaling axis in gastric cancer, we discovered that tRNA synthetase YARS is a novel tumorigenic factor, characterized by its upregulation in tumor-derived specimens, as well as its functions in promoting gastric cancer progression.

摘要

目的: aaRS (氨酰-tRNA 合成酶) 家族成员是控制氨基酰化过程的蛋白质,其中 YARS (tyrosyl-tRNA 合成酶) 催化酪氨酸与其同源 tRNA 结合,在碱性生物合成中起重要作用。几项研究已经证明了 YARS 突变与某些发育异常/疾病之间的关联,然而 YARS 与癌症的联系仍然是未分类的。在本研究中,通过结合计算机模拟、体外和体内研究,我们探讨了 YARS 在胃癌 (GC) 中的表达和功能。 方法: 我们通过参考大型队列在线数据集和患者来源的组织标本,评价了 YARS 在肿瘤和配对正常组织/GC 标本中的分布。在携带 YARS 敲除或过表达的 GC 细胞系中,通过表型/分子实验和 RNA 测序分析评估 YARS 相关变化。 结果: 胃癌组织中 YARS 的转录和蛋白水平均明显高于配对正常组织。YARS 敲除诱导了 GC 细胞系的增殖和侵袭能力的抑制,以及细胞凋亡的增强,而异常上调 YARS 的表达促进了体内胃癌的生长。我们根据 RNA 测序推断 YARS 调节多个癌性信号通路,并通过细胞实验证明 YARS 通过激活 PI3K-Akt 信号促进 GC 进展以及同源重组。 结论: 通过揭示胃癌中 YARS-PI3K-Akt 信号轴的存在,我们发现 tRNA 合成酶 (YARS) 是一种新的致瘤因子,其特点是在肿瘤来源的标本中表达上调。以及其在促进胃癌进展中的功能。

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影响因子:1.71
发表时间:2020-01-28
DOI:10.2217/fon-2019-0649
作者列表:["Jing JJ","Li H","Wang ZY","Zhou H","Sun LP","Yuan Y"]

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翻译标题与摘要 下载文献
影响因子:3.89
发表时间:2020-01-28
DOI:10.1002/jcp.29562
作者列表:["Daryabari SS","Fathi M","Mahdavi M","Moaddab Y","Hosseinpour Feizi MA","Shokoohi B","Safaralizadeh R"]

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