Abstract
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.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,General Medicine
Cited by
26 articles.
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