XRRA1 Targets ATM/CHK1/2-Mediated DNA Repair in Colorectal Cancer

Wang, Wenjun; Guo, Meihua; Xia, Xiaojun; Zhang, Chao; Zeng, Yuan; Wu, Si-Pei

doi:10.1155/2017/5718968

Cited by 9 publications

(11 citation statements)

References 17 publications

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“…CHK2 is a tumour suppressor gene encoding a serine/threonine kinase. It plays a very important role in the regulation of cell cycle checkpoints caused by DNA damage and participates in maintaining genome stability . MDMX, as an inhibitor of p53, could cause the ubiquitination and degradation of p53 .…”

Section: Discussionmentioning

confidence: 99%

Inhibition of MELK produces potential anti‐tumour effects in bladder cancer by inducing G1/S cell cycle arrest via the ATM/CHK2/p53 pathway

Chen

Zhou

Guo

et al. 2019

J Cellular Molecular Medi

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We aimed to investigate the biological function of MELK and the therapeutic potential of OTSSP167 in human bladder cancer (BCa). First, we observed overexpression of MELK in BCa cell lines and tissues and found that it was associated with higher tumour stage and tumour grade, which was consistent with transcriptome analysis.High expression of MELK was significantly correlated with poor prognosis in BCa patients, and MELK was found to have a role in the cell cycle, the G1/S transition in mitosis, and DNA repair and replication. Furthermore, BCa cells presented significantly decreased proliferation capacity following silencing of MELK or treatment with OTSSP167 in vitro and in vivo. Functionally, reduction in MELK or treatment of cells with OTSSP167 could induce cell cycle arrest and could suppress migration. In addition, these treatments could activate phosphorylation of ATM and CHK2, which would be accompanied by down-regulated MDMX, cyclin D1, CDK2 and E2F1; however, p53 and p21 would be activated. Opposite results were observed when MELK expression was induced. Overall, MELK was found to be a novel oncogene in BCa that induces cell cycle arrest via the ATM/CHK2/p53 pathway. OTSSP167 displays potent anti-tumour activities, which may provide a new molecule-based strategy for BCa treatment. K E Y W O R D S bladder cancer, cell cycle, MELK, OTSSP167, p53 | 1805 CHEN Et al.

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Section: Discussionmentioning

confidence: 99%

Inhibition of MELK produces potential anti‐tumour effects in bladder cancer by inducing G1/S cell cycle arrest via the ATM/CHK2/p53 pathway

Chen

Zhou

Guo

et al. 2019

J Cellular Molecular Medi

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“…This gene has been linked to colorectal cancer (CRC). 19 Blocked XRRA1 expression can lead to cell cycle arrest in CRC. Expressed XRRA1 can reduce cell cycle arrest and increase cell proliferation in CRC.…”

Section: Resultsmentioning

confidence: 99%

An application of matrix eQTL to billions hypothesis testing to identify expression quantitative trait loci in genome wide association studies of inflammatory bowel disease

Moradi¹,

Hajihosseini²,

Khodayari-Moez³

et al. 2020

JCPCR

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Introduction: Genome wide association studies (GWAS) have been widely used in recent years to identify new information on genetic variants which are associated with complex trait in many diseases. Advances in identifying the Single Nucleotide Polymorphisms (SNPs) facilitate the study of etiologies of common disorders including cancers, inflammatory bowel diseases (IBD) and colorectal cancer. Variations in gene expression demonstrate that transcript levels of many RNAs behave as heritable quantitative traits. Studying the genetics of gene expression can provide additional power to the roles of GWAS variants. Expression quantitative trait loci (eQTL) mapping links the genome-wide SNPs with RNA expression.Methods: In this study, we performed expression quantitative trait loci (eQTL) analysis using the Matrix eQTL R package. This technique implements matrix covariance calculation and efficiently runs ANOVA and linear regression analysis for eQTL studies. The statistical test determines the association between SNP and gene expression, where the null hypothesis is no association between genotype and phenotypes. False Discovery Rate (FDR) is used to identify significant cis and trans eQTL and adjust for multiple hypothesis testing. Results:We applied matrix eQTL to a real data set consisting of 730,256 SNP and 33,298 RNA for 173 samples. SNPs with minor allele frequency (MAF) less than 0.05 and those violating the Hardy_Weinberg equilibrium (HWE), were excluded from the study. In this study, 15,408 cis eQTL and 27,562 trans eQTL are identified at a FDR less than 0.05, corresponding to p value thresholds of 8e-5 and 1e-8, respectively. Conclusion:We found out that matrix eQTL is a computationally efficient and user friendly method for analysis of eQTL studies. Our application provides insight into the genomic architecture of gene regulation in inflammatory bowel disease (IBD).

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“…It increases the stability of P53 and induces cell cycle arrest in the G 1 phase ( 28 ). However, CHEK2 mutations are very common in several types of cancer, including breast cancer ( 29 ), colorectal cancer ( 30 ) and oral squamous cell carcinoma ( 31 ). Additionally, CHEK2 promotes the progression of various types of cancer, including hepatocellular carcinoma ( 32 ) and colorectal cancer ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

PSMC2, ORC5 and KRTDAP are specific biomarkers for HPV‑negative head and neck squamous cell carcinoma

Zeng

Rong

et al. 2021

Oncol Lett

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The prognosis of patients with human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is poorer than those with HPV-positive HNSCC. The present study aimed to identify novel and specific biomarkers of HPV-negative HNSCC using bioinformatics analysis and associated experiments. The gene expression profiles of HPV-negative HNSCC tissues and corresponding clinical data were downloaded from The Cancer Genome Atlas database and used in a weighted gene co-expression network analysis. Genes in clinically significant co-expression modules were used to construct a protein-protein interaction (PPI) network. The genes demonstrating a high degree score in the PPI network and a high correlation with tumor grade were considered hub genes. The diagnostic value of the hub genes associated with HPV-negative and HPV-positive HNSCC was analyzed using differential expression gene (DEG) analysis, immunohistochemical (IHC) staining and a receiver operating characteristic (ROC) curve analysis. Seven genes [Serrate RNA effector molecule (SRRT), checkpoint kinase 2 (CHEK2), small nuclear ribonucleoprotein polypeptide E (SNRPE), proteasome 26S subunit ATPase 2 (PSMC2), origin recognition complex subunit 5 (ORC5), S100 calcium binding protein A7 and keratinocyte differentiation associated protein (KRTDAP)] were demonstrated to be hub genes in clinically significant co-expression modules. DEG, IHC and ROC curve analyses revealed that SRRT, CHEK2 and SNRPE were significantly upregulated in HPV-negative and HPV-positive HNSCC tissues compared with in adjacent tissues, and these genes demonstrated a high diagnostic value for distinguishing HNSCC tissues. However, PSMC2, ORC5 and KRTDAP were the only differentially expressed genes identified in HPV-negative HNSCC tissues, and these genes demonstrated a high diagnostic value for HPV-negative HNSCC. PSMC2, ORC5 and KRTDAP may therefore serve as novel and specific biomarkers for HPV-negative HNSCC, potentially improving the diagnosis and treatment of patients with HPV-negative HNSCC.

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XRRA1 Targets ATM/CHK1/2-Mediated DNA Repair in Colorectal Cancer

Cited by 9 publications

References 17 publications

Inhibition of MELK produces potential anti‐tumour effects in bladder cancer by inducing G1/S cell cycle arrest via the ATM/CHK2/p53 pathway

Inhibition of MELK produces potential anti‐tumour effects in bladder cancer by inducing G1/S cell cycle arrest via the ATM/CHK2/p53 pathway

An application of matrix eQTL to billions hypothesis testing to identify expression quantitative trait loci in genome wide association studies of inflammatory bowel disease

PSMC2, ORC5 and KRTDAP are specific biomarkers for HPV‑negative head and neck squamous cell carcinoma

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