| Title | YARS as an oncogenic protein that promotes gastric cancer progression through activating PI3K-Akt signaling |
| Authors | Zhang, Cheng Lin, Xiaoting Zhao, Qian Wang, Yakun Jiang, Fangli Ji, Congcong Li, Yanyan Gao, Jing Li, Jian Shen, Lin |
| Affiliation | Peking Univ, Dept Gastrointestinal Oncol, Key Lab Carcinogenesis & Translat Res, Minist Educ Beijing,Canc Hosp & Inst, 52 Fucheng Rd, Beijing 100142, Peoples R China Xiamen Univ, Canc Hosp, Affiliated Hosp 1, Dept Med Oncol, Xiamen, Peoples R China Fujian Med Univ, Dept Clin Med, Fuzhou, Peoples R China Xiamen Univ, Xiamen Key Lab Antitumor Drug Transformat Res, Affiliated Hosp 1, Xiamen, Peoples R China Chinese Acad Med Sci & Peking Union Med Coll, Natl Clin Res Ctr Canc, Canc Hosp, Natl Canc Ctr, Shenzhen 518116, Peoples R China Chinese Acad Med Sci & Peking Union Med Coll, Shenzhen Hosp, Shenzhen 518116, Peoples R China |
| Keywords | TRANSFER-RNA SYNTHETASE HOMOLOGOUS RECOMBINATION DEFICIENCY GENE-EXPRESSION PROSTATE-CANCER BREAST-CANCER MUTATIONS CONTRIBUTES VARIANT |
| Issue Date | Feb-2020 |
| Publisher | JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY |
| 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. |
| URI | http://hdl.handle.net/20.500.11897/586898 |
| ISSN | 0171-5216 |
| DOI | 10.1007/s00432-019-03115-7 |
| Indexed | SCI(E) |
| Appears in Collections: | 北京肿瘤医院 |
