Potentially functional polymorphisms in aminoacyl-tRNA synthetases genes are associated with breast cancer risk in a Chinese population

He, Yunjie; Gong, Jianhang; Wang, Yanru; Qin, Zhenzhen; Jiang, Yue; Ma, Hongxia; Jin, Guangfu; Chen, Jiaping; Hu, Zhibin; Guan, Xiaoxiang; Shen, Hongbing

doi:10.1002/mc.22128

Cited by 15 publications

(16 citation statements)

References 48 publications

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“…Several studies have now shown that for YARS, GARS, and AARS loss of aminoacylation is, in fact, not necessary for the disease to develop [Antonellis and Green, 2006; Nangle et al, ; Storkebaum et al, ; McLaughlin et al, ]. Instead, these and other recent studies suggest a mechanism related to either a dominant‐negative effect on the holoenzyme or interference with secondary functions [Jordanova et al, ; Motley et al, ; Vester et al, ; Grice et al, ; He et al, ].…”

Section: Discussionmentioning

confidence: 99%

A novel multisystem disease associated with recessive mutations in the tyrosyl‐tRNA synthetase (YARS) gene

Nowaczyk

Huang

Tarnopolsky

et al. 2016

American J of Med Genetics Pt A

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Aminoacyl-tRNA synthetases (ARSs) are a group of ubiquitously expressed enzymes that are best known for their function in the first step of protein translation but have been increasingly associated with secondary functions including transcription and translation control and extracellular signaling. Mutations in numerous ARSs have been linked to a growing number of both autosomal dominant and autosomal recessive human diseases. The tyrosyl-tRNA synthetase (YARS) links the amino acid tyrosine to its cognate tRNA. We report two siblings who presented with failure to thrive (FTT), hypertriglyceridemia, developmental delay, liver dysfunction, lung cysts, and abnormal subcortical white matter. Using exome sequencing the siblings were found to harbor bi-allelic pathogenic-appearing variants within the YARS gene (NM_003680.3):c.638C>T p.(Pro213Leu) and c.1573G>A p.(Gly525Arg). These YARS variants occur in the catalytic domain and the C-terminal domain, respectively. Mutations in YARS have been previously associated with an autosomal dominant form of Charcot-Marie-Tooth (CMT); our findings suggest the disease spectrum associated with YARS dysregulation is broader than peripheral neuropathy. © 2016 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

A novel multisystem disease associated with recessive mutations in the tyrosyl‐tRNA synthetase (YARS) gene

Nowaczyk

Huang

Tarnopolsky

et al. 2016

American J of Med Genetics Pt A

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“…On the other hand, the upregulation of aaRSs, including YARS, was observed in several types of cancer (Guo et al 2010;Hsu et al 2019), while polymorphisms in aaRS genes were reported to be associated with breast cancer risk (He et al 2015). Emerging studies also implicated the involvement of aaRSs with multiple pathway networks through constituting the multi-tRNA synthetase complex (MSC) (Hyeon et al 2019) and raised the possibility of aminoacyl-tRNA synthetases as therapeutic targets against autoimmune diseases, rare diseases, and even cancer (Kwon et al 2019).…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Lin

Zhao

et al. 2020

J Cancer Res Clin Oncol

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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 RNAsequencing 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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“…It is estimated that about 3.2 million people will be diagnosed with breast cancer each year by 2050 worldwide [3]. Breast cancer is a complex and multifactorial disease, which is affected by combined effects of environmental and inherited factors [4]. It is characterized by starting with hyperplasia, in distinct steps, in situ ductal and invasive carcinoma then evolv-ing into a deadly metastatic disease [5].…”

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confidence: 99%

Evaluation of the efficacy of neoadjuvant chemotherapy for breast cancer using diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging

Xu¹,

Zhang²

2017

neo

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This study aims to investigate the predictive values of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in evaluating the efficacy of neoadjuvant chemotherapy (NAC) for breast cancer. Between September 2011 and December 2014, a total of 174 patients with locally advanced breast cancer treated with NAC were selected for this study. Conventional CT and MRI examinations (DWI and DCE-MRI) were performed in all patients before NAC (T0), after the first course (T1) and after the whole course (T2) of NAC. According to the response evaluation criteria in solid tumors (RECIST), patients were divided into the effective [complete response (CR) + partial response (PR)] and ineffective groups [stable disease (SD) + disease progression (DP)]. The Apparent diffusion coefficient (ADC), maximum tumor diameter, the early-phase enhancement rate (Ee), maximal enhanced rate of tumor (E max), maximal linear slope (S max), maximal excretion rate (E wash), signal intensity (SI), maximal signal rise velocity (V max) and area under the curve (AUC) of Cho before and after NAC were calculated. Receiver operating characteristic (ROC) curve was drawn and the AUC of change rate of ADC values and semi-quantitative parameter were utilized to analyze the diagnostic performance of them for evaluating the efficacy of NAC for breast cancer. There were 135 patients in the effective group, with 52 cases of CR and 83 cases of PR; 39 patients were in the ineffective group, with 14 cases of PD and 25 cases of SD. The effective rate of NAC for breast cancer was 77.6%. The ADC values of the two groups significantly increased but the maximum tumor diameter, E e, E max, S max, E wash and AUC of Cho greatly decreased. The effective group had higher ADC values, its change rate and tumor regression rate than the ineffective group. However, the maximum tumor diameter, E e, E max, S max, E wash, AUC of Cho, SI and V max in the effective group were remarkably lower than those in the ineffective group. The change rate of ADC mean achieved the highest evaluation efficiency with AUC of 0.920, sensitivity of 80.0% and specificity of 94.9%. The optimal critical value was 36.49 (× 10-3mm2/s). In conclusion, these results demonstrated that the change rate of ADC mean values and E e could be promising tools for evaluating the efficacy of NAC in patients with breast cancer.

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Potentially functional polymorphisms in aminoacyl-tRNA synthetases genes are associated with breast cancer risk in a Chinese population

Cited by 15 publications

References 48 publications

A novel multisystem disease associated with recessive mutations in the tyrosyl‐tRNA synthetase (YARS) gene

A novel multisystem disease associated with recessive mutations in the tyrosyl‐tRNA synthetase (YARS) gene

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

Evaluation of the efficacy of neoadjuvant chemotherapy for breast cancer using diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging

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