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Journal of Cancer Research and Clinical Oncology

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Open Access 01-02-2020 | Gastric Cancer | Original Article – Cancer Research

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

Authors: Cheng Zhang, Xiaoting Lin, Qian Zhao, Yakun Wang, Fangli Jiang, Congcong Ji, Yanyan Li, Jing Gao, Jian Li, Lin Shen

Published in: Journal of Cancer Research and Clinical Oncology | Issue 2/2020

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.

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Title: YARS as an oncogenic protein that promotes gastric cancer progression through activating PI3K-Akt signaling
Authors: Cheng Zhang
Xiaoting Lin
Qian Zhao
Yakun Wang
Fangli Jiang
Congcong Ji
Yanyan Li
Jing Gao
Jian Li
Lin Shen
Publication date: 01-02-2020
Publisher: Springer Berlin Heidelberg
Keywords: Gastric Cancer
Gastric Cancer
Published in: Journal of Cancer Research and Clinical Oncology / Issue 2/2020
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-019-03115-7

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Conclusions

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