Dataset Information

Identification of molecular correlations of RBM8A with autophagy in Alzheimer's disease.

ABSTRACT: Our previous studies revealed RBM8A may play a role in various progressive neurological diseases. The present study aimed to explore the role of RBM8A in Alzheimer's disease (AD). RBM8A is significantly down-regulated in AD. Interestingly, 9186 differentially expressed genes are overlapped from comparisons of AD versus control and RBM8A-low versus RBM8A-high. Weight gene correlation analysis was performed and 9 functional modules were identified. Modules positively correlated with AD and RBM8A-low are significantly involved in the RAP1 signaling pathway, PI3K-AKT signaling pathway, hematopoietic cell lineage, autophagy and APELIN signaling pathway. Fifteen genes (RBM8A, RHBDF2, TNFRSF10B, ACP1, ANKRD39, CA10, CAMK4, CBLN4, LOC284214, NOVA1, PAK1, PPEF1, RGS4, TCEB1 and TMEM118) are identified as hub genes, and the hub gene-based LASSO model can accurately predict the occurrence of AD (AUC = 0.948). Moreover, the RBM8A-module-pathway network was constructed, and low expression of RBM8A down-regulates multiple module genes, including FIP200, Beclin 1, NRBF2, VPS15 and ATG12, which composes key complexes of autophagy. Thus, our study supports that low expression of RBM8A correlates with the decrease of the components of key complexes in autophagy, which could potentially contribute to pathophysiological changes of AD.

SUBMITTER: Zou D

PROVIDER: S-EPMC6932873 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Identification of molecular correlations of RBM8A with autophagy in Alzheimer's disease.

Zou Donghua D Li Rongjie R Huang Xiaohua X Chen Guoying G Liu Ying Y Meng Youshi Y Wang Yimei Y Wu Yuan Y Wu Yuan Y Mao Yingwei Y

Aging 20191209 23

Our previous studies revealed RBM8A may play a role in various progressive neurological diseases. The present study aimed to explore the role of RBM8A in Alzheimer's disease (AD). RBM8A is significantly down-regulated in AD. Interestingly, 9186 differentially expressed genes are overlapped from comparisons of AD versus control and RBM8A-low versus RBM8A-high. Weight gene correlation analysis was performed and 9 functional modules were identified. Modules positively correlated with AD and RBM8A-l ...[more]

PMID: 31816601

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Project description:A growing body of evidence suggests that dysbiosis of the human gut microbiota is associated with neurodegenerative diseases like Alzheimer's disease (AD) via neuroinflammatory processes across the microbiota-gut-brain axis. The gut microbiota affects brain health through the secretion of toxins and short-chain fatty acids, which modulates gut permeability and numerous immune functions. Observational studies indicate that AD patients have reduced microbiome diversity, which could contribute to the pathogenesis of the disease. Uncovering the genetic basis of microbial abundance and its effect on AD could suggest lifestyle changes that may reduce an individual's risk for the disease. Using the largest genome-wide association study of gut microbiota genera from the MiBioGen consortium, we used polygenic risk score (PRS) analyses with the "best-fit" model implemented in PRSice-2 and determined the genetic correlation between 119 genera and AD in a discovery sample (ADc12 case/control: 1278/1293). To confirm the results from the discovery sample, we next repeated the PRS analysis in a replication sample (GenADA case/control: 799/778) and then performed a meta-analysis with the PRS results from both samples. Finally, we conducted a linear regression analysis to assess the correlation between the PRSs for the significant genera and the APOE genotypes. In the discovery sample, 20 gut microbiota genera were initially identified as genetically associated with AD case/control status. Of these 20, three genera (Eubacterium fissicatena as a protective factor, Collinsella, and Veillonella as a risk factor) were independently significant in the replication sample. Meta-analysis with discovery and replication samples confirmed that ten genera had a significant correlation with AD, four of which were significantly associated with the APOE rs429358 risk allele in a direction consistent with their protective/risk designation in AD association. Notably, the proinflammatory genus Collinsella, identified as a risk factor for AD, was positively correlated with the APOE rs429358 risk allele in both samples. Overall, the host genetic factors influencing the abundance of ten genera are significantly associated with AD, suggesting that these genera may serve as biomarkers and targets for AD treatment and intervention. Our results highlight that proinflammatory gut microbiota might promote AD development through interaction with APOE. Larger datasets and functional studies are required to understand their causal relationships.

Project description:Background: Glioblastoma (GBM) is the most invasive brain tumors, and it is associated with high rates of recurrence and mortality. The purpose of this study was to investigate the expression of RBM8A in GBM and the potential influence of its expression on the disease. Methods: Levels of RBM8A mRNA in GBM patients and controls were examined in The Cancer Genome Atlas (TCGA), GSE16011 and GSE90604 databases. GBM samples in TCGA were divided into RBM8Ahigh and RBM8Alow groups. Differentially expressed genes (DEGs) between GBM patients and controls were identified, as were DEGs between RBM8Ahigh and RBM8Alow groups. DEGs common to both of these comparisons were analyzed for coexpression and regression analyses. In addition, we identified potential effects of RBM8A on competing endogenous RNAs, immune cell infiltration, methylation modifications, and somatic mutations. Results: RBM8A is expressed at significantly higher levels in GBM than control samples, and its level correlates with tumor purity. We identified a total of 488 mRNAs that differed between GBM and controls as well as between RBM8Ahigh and RBM8Alow groups, which enrichment analysis revealed to be associated mainly with neuroblast proliferation, and T cell immune responses. We identified 174 mRNAs that gave areas under the receiver operating characteristic curve >0.7 among coexpression module genes, of which 13 were significantly associated with overall survival of GBM patients. We integrated 11 candidate mRNAs through LASSO algorithm, then nomogram, risk score, and decision curve analyses were analyzed. We found that RBM8A may compete with DLEU1 for binding to miR-128-1-5p, and aberrant RBM8A expression was associations with tumor infiltration by immune cells. Some mRNAs associated with GBM prognosis also appear to be methylated or mutated. Conclusions: Our study strongly links RBM8A expression to GBM pathobiology and patient prognosis. The candidate mRNAs identified here may lead to therapeutic targets against the disease.

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Identification of molecular correlations of RBM8A with autophagy in Alzheimer's disease.

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Identification of molecular correlations of RBM8A with autophagy in Alzheimer's disease.

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