Genetic predisposition to B-cell acute lymphoblastic leukemia at 14q11.2 is mediated by a CEBPE promoter polymorphism

Studd, James B.; Yang, Minjun; Li, Zhenhua; Vijayakrishnan, Jayaram; Lü, Yi; Yeoh, Allen Eng Juh; Paulsson, Kajsa; Houlston, Richard S.

doi:10.1038/s41375-018-0184-z

Cited by 23 publications

(34 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, rs2239630G/A is present in the promoter of the CCAT enhancer-binding protein epsilon (CEBPE) gene. The rs2239630A allele can enhance promoter activity and CEBPE expression and is associated with the risk of acute lymphoblastic leukemia [21]. The Matrix metalloproteinase (MMP-9) gene promoter polymorphism − 1562C/T regulates its transcriptional activity and affects the course of thyroid carcinoma [22].…”

Section: Discussionmentioning

confidence: 99%

Functional polymorphisms and transcriptional analysis in the 5' region of the human serotonin receptor 1B gene (HTR1B) and their associations with psychiatric disorders

Xia

Ding

Xuan

et al. 2020

Preprint

View full text Add to dashboard Cite

Background The 5-hydroxytryptamine 1B receptor (5-HT1B) plays an essential role in the serotonin (5-HT) system and is widely involved in a variety of brain activities. HTR1B is the gene encoding 5-HT1B. Genome-wide association studies have shown that HTR1B polymorphisms are closely related to multiple mental and behavioral disorders; however, the functional mechanisms underlying these associations are unknown. This study investigated the effect of several HTR1B haplotypes on reporter protein expression levels in vitro and the functional sequences in the 5' regulatory region of HTR1B to determine their potential association with mental and behavioral disorders.MethodsSix haplotypes consisting of rs4140535, rs1778258, rs17273700, rs1228814, rs11568817, and rs130058 and several truncated fragments of the 5' regulatory region of HTR1B were transfected into SK-N-SH and HEK-293 cells. The relative fluorescence intensities of the different haplotypes and truncated fragments were detected using a dual-luciferase reporter assay system.Results Compared to the major haplotype T-G-T-C-T-A, the relative fluorescence intensities of haplotypes C-A-T-C-T-A, C-G-T-C-T-A, C-G-C-A-G-T, and C-G-T-A-T-A were significantly lower, and that of haplotype C-G-C-A-G-A was significantly higher. Furthermore, the effects of the rs4140535T allele, the rs17273700C-rs11568817G linkage combination, and the rs1228814A allele made their relative fluorescence intensities significantly higher than their counterparts at each locus. Conversely, the rs1778258A and rs130058T alleles decreased the relative fluorescence intensities. In addition, we found that regions from -1587 to -1371 bp (TSS, +1), -1149 to -894 bp, -39 to +130 bp, +130 to +341 bp, and +341 to +505 bp upregulated gene expression. In contrast, regions -603 to -316 bp and +130 to +341 bp downregulated gene expression. Region +341 to +505 bp contained the core promoter region and played a decisive role in gene transcription.Conclusions HTR1B 5' regulatory region polymorphisms have regulatory effects on gene expression and potential correlate with several pathology and physiology conditions. This study suggests that the core promoter sequence of HTR1B is located in region +341~+505 bp. Regions -1587 to -1371 bp, -1149 to -894 bp, -603 to -316 bp, -39 to +130 bp, and +130 to +341 bp contain functional sequences that can promote or suppress the HTR1B gene expression.

show abstract

Section: Discussionmentioning

confidence: 99%

Functional polymorphisms and transcriptional analysis in the 5' region of the human serotonin receptor 1B gene (HTR1B) and their associations with psychiatric disorders

Xia

Ding

Xuan

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Moreover, double homeobox A pseudogene 10, located in chr14q11.2, promotes an aggressive phenotype by binding lysine-specific histone demethylase 1 and repressing large tumor suppressor kinase 2 and Ras-related glycolysis inhibitor and calcium channel regulator expression levels in NSCLC (17). Furthermore, previous studies have revealed that chr14q11.2 may participate in cancer development (18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

Epididymal protein 3A is upregulated and promotes cell proliferation in non‑small cell lung cancer

Xing

Pan

et al. 2020

Oncol Lett

View full text Add to dashboard Cite

Lung cancer is one of the most common cancer types and a major contributor to cancer-associated mortalities worldwide. The aim of the present study was to investigate the function of the epididymal protein 3A (EDDM3A) in non-small cell lung cancer (NSCLC). Data from patients with NSCLC were retrieved from The Cancer Genome Atlas and analyzed, and the differences in EDDM3A expression level between 30 NSCLC tissues and matched adjacent non-tumor tissues (>5 cm) were assessed via tissue microarray analysis. It was revealed that, compared with adjacent non-tumor tissues, EDDM3A expression was significantly increased in NSCLC tissues (P=4.19x10-2). To knock down EDDM3A expression in a human NSCLC cell line, lentivirus-mediated short hairpin RNAs (shRNAs) were used, and the knockdown efficiency was assessed via reverse transcription-quantitative PCR and western blotting. Moreover, cell proliferation was evaluated with an MTT assay and Celigo imaging cytometry. In addition, cell apoptosis was detected by Annexin V staining. It was demonstrated that knockdown of EDDM3A inhibited the proliferation of A549 cells. Furthermore, compared with the control group, the apoptotic rate of the EDDM3A-shRNA group was significantly higher. Collectively, the present results indicate the potential role of EDDM3A in NSCL and suggest that EDDM3A may represent a potent therapeutic target for treating patients with NSCLC.

show abstract

“…An interesting example of SNPs, associated with susceptibility to cALL and affecting metabolic genes indirectly, is an SNP located in the promoter of the transcription factor CEBPE which activates the promoter leading to upregulation of CEBPE levels. The transcription factor, in turn, upregulates the expression of ETC and energy production genes 50 …”

Section: Cell Metabolism In Callmentioning

confidence: 99%

Metabolic reprogramming in childhood acute lymphoblastic leukemia

Sbirkov

Burnusuzov

Sarafian

2020

Pediatric Blood & Cancer

View full text Add to dashboard Cite

The first observations of altered metabolism in malignant cells were made nearly 100 years ago and therapeutic strategies targeting cell metabolism have been in clinical use for several decades. In this review, we summarize our current understanding of cell metabolism dysregulation in childhood acute lymphoblastic leukemia (cALL). Reprogramming of cellular bioenergetic processes can be expected in the three distinct stages of cALL: at diagnosis, during standard chemotherapy, and in cases of relapse. Upregulation of glycolysis, dependency on anaplerotic energy sources, and activation of the electron transport chain have all been observed in cALL.While the current treatment strategies are tackling some of these aberrations, cALL cells are likely to be able to rewire their metabolism in order to escape therapy, which may contribute to a refractory disease and relapse. Finally, here we focus on novel therapeutic approaches emerging from our evolving understanding of the alterations of different metabolic networks in lymphoblasts. K E Y W O R D SBioenergetics, cALL, cell metabolism, therapy

show abstract

Genetic predisposition to B-cell acute lymphoblastic leukemia at 14q11.2 is mediated by a CEBPE promoter polymorphism

Cited by 23 publications

References 69 publications

Functional polymorphisms and transcriptional analysis in the 5' region of the human serotonin receptor 1B gene (HTR1B) and their associations with psychiatric disorders

Functional polymorphisms and transcriptional analysis in the 5' region of the human serotonin receptor 1B gene (HTR1B) and their associations with psychiatric disorders

Epididymal protein 3A is upregulated and promotes cell proliferation in non‑small cell lung cancer

Metabolic reprogramming in childhood acute lymphoblastic leukemia

Contact Info

Product

Resources

About