Dataset Information

Co-expression Network Revealed Roles of RNA m⁶A Methylation in Human β-Cell of Type 2 Diabetes Mellitus.

ABSTRACT: RNA m⁶A methylation plays an important role in the pathogenesis of type 2 diabetes mellitus (T2DM). RNA modifications and RNA-modifying regulators have recently emerged as critical factors involved in β-cell function and insulin resistance, including "writers," "erasers," and "readers." However, their key roles in regulating gene expression in T2DM remain unclear. The construction of co-expression network could provide a cue to resolve this complex regulatory pathway. We collected the transcriptome datasets of β-cell in diabetic patients, calculated the partial correlation coefficient, excluded the influence from control variables of diabetes related genes, and identified the genes significantly co-expressed with m⁶A regulators. A total of 985 genes co-expressed with m⁶A regulators (Co-m⁶AR) were identified, which were enriched in metabolic process, MAPK and EGFR signaling pathways. Some of them have been confirmed to play a pivotal role in T2DM, including CCNL2, CSAD, COX5A, GAB2, and MIRLET7I, etc. Further, we analyzed the m⁶A modification characteristics of Co-m⁶AR in β-cell and identified 228 Co-m⁶AR containing m⁶A methylation sites, involving in several key signaling pathways regulating T2DM. We finally screened out 13 eQTL-SNPs localized in Co-m⁶ARs, and 4 have been reported strongly associated with diabetes, including GAB2, LMNB2, XAB2, and RBM39. This co-expression analysis provides important information to reveal the potential regulatory mechanism of RNA m⁶A methylation in T2DM.

SUBMITTER: Chen C

PROVIDER: S-EPMC8168466 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Co-expression Network Revealed Roles of RNA m<sup>6</sup>A Methylation in Human β-Cell of Type 2 Diabetes Mellitus.

Chen Cong C Xiang Qing Q Liu Weilin W Liang Shengxiang S Yang Minguang M Tao Jing J

Frontiers in cell and developmental biology 20210518

RNA m<sup>6</sup>A methylation plays an important role in the pathogenesis of type 2 diabetes mellitus (T2DM). RNA modifications and RNA-modifying regulators have recently emerged as critical factors involved in β-cell function and insulin resistance, including "writers," "erasers," and "readers." However, their key roles in regulating gene expression in T2DM remain unclear. The construction of co-expression network could provide a cue to resolve this complex regulatory pathway. We collected the ...[more]

PMID: 34084770

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Project description:Angiopoietin like protein 8 (ANGPTL8) is a newly identified hormone with unique nature due to its ability to regulate both glucose and lipid metabolic pathways. It is characterized as an important molecular player of insulin induced nutrient storage and utilization pathway during fasting to re-feeding metabolic transition. Several studies have contributed to increase our knowledge regarding its function and mechanism of action. Moreover, its altered expression levels have been observed in Insulin Resistance, Diabetes Mellitus (Types I & II) and Non Alcohlic Fatty Liver Disease emphasizing its assessment as a drug target. However, there is still a great deal of information that remains to be investigated including its associated biological processes, partner proteins in these processes, its regulators and its association with metabolic pathogenesis. In the current study, the analysis of a transcriptomic data set was performed for functional assessment of ANGPTL8 in liver. Weighted Gene Co-expression Network Analysis coupled with pathway analysis tools was performed to identify genes that are significantly co-expressed with ANGPTL8 in liver and investigate their presence in biological pathways. Gene ontology term enrichment analysis was performed to select the gene ontology classes that over-represent the hepatic ANGPTL8-co-expressed genes. Moreover, the presence of diabetes linked SNPs within the genes set co-expressed with ANGPTL8 was investigated. The co-expressed genes of ANGPTL8 identified in this study (n = 460) provides narrowed down list of molecular targets which are either co-regulated with it and/or might be regulation partners at different levels of interaction. These results are coherent with previously demonstrated roles and regulators of ANGPTL8. Specifically, thirteen co-expressed genes (MAPK8, CYP3A4, PIK3R2, PIK3R4,PRKAB2, G6PC, MAP3K11, FLOT1, PIK3C2G, SHC1, SLC16A2, and RAPGEF1) are also present in the literature curated pathway of ANGPTL8 (WP3915). Moreover, the gene-SNP analysis of highly associated biological processes with ANGPTL8 revealed significant genetic signals associated to Diabetes Mellitus and similar phenotypic traits. It provides meaningful insights on the influencing genes involved and co-expressed in these pathways. Findings of this study have implications in functional characterization of ANGPTL8 with emphasis on the identified genes and pathways and their possible involvement in the pathogenesis of Diabetes Mellitus and Insulin Resistance.

Dataset Information

Co-expression Network Revealed Roles of RNA m⁶A Methylation in Human β-Cell of Type 2 Diabetes Mellitus.

Publications

Co-expression Network Revealed Roles of RNA m<sup>6</sup>A Methylation in Human β-Cell of Type 2 Diabetes Mellitus.

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Dataset Information

Co-expression Network Revealed Roles of RNA m6A Methylation in Human β-Cell of Type 2 Diabetes Mellitus.

Publications

Co-expression Network Revealed Roles of RNA m<sup>6</sup>A Methylation in Human β-Cell of Type 2 Diabetes Mellitus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Co-expression Network Revealed Roles of RNA m⁶A Methylation in Human β-Cell of Type 2 Diabetes Mellitus.