DNA Methylation-Specific Analysis of G Protein-Coupled Receptor-Related Genes in Pan-Cancer

Zhang, Mengyan; Zhao, Jiyun; Dong, Huili; Xue, Weilan; Xing, Jie; Liu, Ting; Yu, Xiuwen; Gu, Yue; Sun, Baoqing; Lu, Haibo; Zhang, Yan

doi:10.3390/genes13071213

Cited by 4 publications

(2 citation statements)

References 31 publications

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“…The hypothalamic-pituitary–gonadal (HPG) axis in humans comprises at least six GPCRs whose genetic defects, alone or in combination with other gene variants, lead to puberty disorders [ 65 ]. Although alterations in the methylation of GPCR-associated signaling have been reported so far mainly in the development of certain types of tumors [ 66 – 68 ], epigenetic modifications of this pathway could also be linked to normal or early pubertal development [ 69 ]. One example is the different methylation, found during the normal pubertal transition, of the relaxin signaling pathway, which, acting through GPCRs, seems to be closely related to connective tissue remodeling, which affects the female reproductive system by promoting the growth of the cervix, uterus and mammary gland [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

Methylome analysis in girls with idiopathic central precocious puberty

Palumbo,

Cirillo

et al. 2024

Clin Epigenet

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Background Genetic and environmental factors are implicated in many developmental processes. Recent evidence, however, has suggested that epigenetic changes may also influence the onset of puberty or the susceptibility to a wide range of diseases later in life. The present study aims to investigate changes in genomic DNA methylation profiles associated with pubertal onset analyzing human peripheral blood leukocytes from three different groups of subjects: 19 girls with central precocious puberty (CPP), 14 healthy prepubertal girls matched by age and 13 healthy pubertal girls matched by pubertal stage. For this purpose, the comparisons were performed between pre- and pubertal controls to identify changes in normal pubertal transition and CPP versus pre- and pubertal controls. Results Analysis of methylation changes associated with normal pubertal transition identified 1006 differentially methylated CpG sites, 86% of them were found to be hypermethylated in prepubertal controls. Some of these CpG sites reside in genes associated with the age of menarche or transcription factors involved in the process of pubertal development. Analysis of methylome profiles in CPP patients showed 65% and 55% hypomethylated CpG sites compared with prepubertal and pubertal controls, respectively. In addition, interestingly, our results revealed the presence of 43 differentially methylated genes coding for zinc finger (ZNF) proteins. Gene ontology and IPA analysis performed in the three groups studied revealed significant enrichment of them in some pathways related to neuronal communication (semaphorin and gustation pathways), estrogens action, some cancers (particularly breast and ovarian) or metabolism (particularly sirtuin). Conclusions The different methylation profiles of girls with normal and precocious puberty indicate that regulation of the pubertal process in humans is associated with specific epigenetic changes. Differentially methylated genes include ZNF genes that may play a role in developmental control. In addition, our data highlight changes in the methylation status of genes involved in signaling pathways that determine the migration and function of GnRH neurons and the onset of metabolic and neoplastic diseases that may be associated with CPP in later life.

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Section: Discussionmentioning

confidence: 99%

Methylome analysis in girls with idiopathic central precocious puberty

Palumbo,

Cirillo

et al. 2024

Clin Epigenet

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“…These findings indicated that the regulation of SFXN3 in tumors is multifaceted. DNA hypermethylation occurs in multiple genes, some of which are associated with G-protein-coupled receptors, appear in many cancers, and affect the efficiency of chemotherapy drugs [ 40 , 41 ]. Some tumor suppressor genes are affected by hypermethylation and promote tumor genesis and invasion through the ERK signaling pathway [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

SFXN3 is Associated with Poor Clinical Outcomes and Sensitivity to the Hypomethylating Therapy in Non-M3 Acute Myeloid Leukemia Patients

Xia

Yang

Dong

et al. 2023

CGT

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Background: DNA hypermethylation plays a critical role in the occurrence and progression of acute myeloid leukemia (AML). The mitochondrial serine transporter, SFXN3, is vital for one-carbon metabolism and DNA methylation. However, the impact of SFXN3 on the occurrence and progression of AML has not been reported yet. Objective: In this study, we hypothesized that SFXN3 indicates a poor prognosis and suggested tailored treatment for AML patients. Methods: We used GEPIA and TCGA repository data to analyze the expression of SFXN3 and its correlation with survival in AML patients. RT-qPCR was used to detect the SFXN3 level in our enrolled AML patients and volunteers. Additionally, Whole Genome Bisulfite Sequencing (WGBS) was used to detect the genomic methylation level in individuals. Results: Through the TCGA and GEPIA databases, we found that SFXN3 was enriched in AML patients, predicting shorter survival. Furthermore, we confirmed that SFXN3 was primarily over-expressed in AML patients, especially non-M3 patients, and that high SFXN3 in non-M3 AML patients was found to be associated with poor outcomes and frequent blast cells. Interestingly, non-M3 AML patients with high SFXN3 levels who received hypomethylating therapy showed a higher CR ratio. Finally, we found that SFXN3 could promote DNA methylation at transcription start sites (TSS) in non-M3 AML patients. These sites were found to be clustered in multiple vital cell functions and frequently accompanied by mutations in DNMT3A and NPM1. Conclusion: In conclusion, SXFN3 plays an important role in the progression and hypermethylation in non-M3 AML patients and could be a potential biomarker for indicating a high CR rate for hypomethylating therapy.

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