Identification of MKNK1 and TOP3A as ovarian endometriosis risk-associated genes using integrative genomic analyses and functional experiments

Huang, Yizhou; Luo, Jie; Zhang, Yue; Zhang, Tao; Fei, Xiangwei; Chen, Liqing; Zhu, Yingfan; Li, Songyue; Zhou, Caiyun; Xu, Kang; Ma, Yunlong; Lin, Jizhen; Zhou, Jianhong

doi:10.1016/j.csbj.2023.02.001

Cited by 6 publications

(3 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was found that in ATRX wild-type pediatric osteosarcomas with alternative lengthening of telomeres (ALT), TOP3A is required for proper BLM localization, and TOP3A amplification promotes ALT DNA synthesis [ 129 ]. Recent large-scale genome-wide association studies (GWAS) and functional studies identified TOP3A as one of the ovarian endometriosis risk-associated genes, possibly due to the role of DNA repair and homologous recombination in endometriosis [ 130 ].…”

Section: Physiological Functions Of Type Ia Topoisomerasesmentioning

confidence: 99%

Variation of Structure and Cellular Functions of Type IA Topoisomerases across the Tree of Life

Tan,

Tse-Dinh

2024

Cells

View full text Add to dashboard Cite

Topoisomerases regulate the topological state of cellular genomes to prevent impediments to vital cellular processes, including replication and transcription from suboptimal supercoiling of double-stranded DNA, and to untangle topological barriers generated as replication or recombination intermediates. The subfamily of type IA topoisomerases are the only topoisomerases that can alter the interlinking of both DNA and RNA. In this article, we provide a review of the mechanisms by which four highly conserved N-terminal protein domains fold into a toroidal structure, enabling cleavage and religation of a single strand of DNA or RNA. We also explore how these conserved domains can be combined with numerous non-conserved protein sequences located in the C-terminal domains to form a diverse range of type IA topoisomerases in Archaea, Bacteria, and Eukarya. There is at least one type IA topoisomerase present in nearly every free-living organism. The variation in C-terminal domain sequences and interacting partners such as helicases enable type IA topoisomerases to conduct important cellular functions that require the passage of nucleic acids through the break of a single-strand DNA or RNA that is held by the conserved N-terminal toroidal domains. In addition, this review will exam a range of human genetic disorders that have been linked to the malfunction of type IA topoisomerase.

show abstract

Section: Physiological Functions Of Type Ia Topoisomerasesmentioning

confidence: 99%

Variation of Structure and Cellular Functions of Type IA Topoisomerases across the Tree of Life

Tan,

Tse-Dinh

2024

Cells

View full text Add to dashboard Cite

show abstract

“…All fresh fecal samples were stored in − 80 °C for subsequent processing and sequencing. Pre-operative blood samples for 50 of these participants were drawn and stored in PAXgene blood RNA tubes at -80 °C before further processing [84].…”

Section: Study Participants and Sample Collectionmentioning

confidence: 99%

Alterations in gut microbiota and host transcriptome of patients with coronary artery disease

Chen,

Mou,

et al. 2023

BMC Microbiol

Self Cite

View full text Add to dashboard Cite

Background Coronary artery disease (CAD) is a widespread heart condition caused by atherosclerosis and influences millions of people worldwide. Early detection of CAD is challenging due to the lack of specific biomarkers. The gut microbiota and host-microbiota interactions have been well documented to affect human health. However, investigation that reveals the role of gut microbes in CAD is still limited. This study aims to uncover the synergistic effects of host genes and gut microbes associated with CAD through integrative genomic analyses. Results Herein, we collected 52 fecal and 50 blood samples from CAD patients and matched controls, and performed amplicon and transcriptomic sequencing on these samples, respectively. By comparing CAD patients with health controls, we found that dysregulated gut microbes were significantly associated with CAD. By leveraging the Random Forest method, we found that combining 20 bacteria and 30 gene biomarkers could distinguish CAD patients from health controls with a high performance (AUC = 0.92). We observed that there existed prominent associations of gut microbes with several clinical indices relevant to heart functions. Integration analysis revealed that CAD-relevant gut microbe genus Fusicatenibacter was associated with expression of CAD-risk genes, such as GBP2, MLKL, and CPR65, which is in line with previous evidence (Tang et al., Nat Rev Cardiol 16:137-154, 2019; Kummen et al., J Am Coll Cardiol 71:1184-1186, 2018). In addition, the upregulation of immune-related pathways in CAD patients were identified to be primarily associated with higher abundance of genus Blautia, Eubacterium, Fusicatenibacter, and Monoglobus. Conclusions Our results highlight that dysregulated gut microbes contribute risk to CAD by interacting with host genes. These identified microbes and interacted risk genes may have high potentials as biomarkers for CAD.

show abstract

“…Pre-operative blood samples for these 54 participants were drawn and stored in PAXgene blood RNA tubes at -80°C before further processing [76]. During the hospitalization period, these subjects were educated and instructed on collecting fecal samples.…”

Section: Study Participants and Sample Collectionmentioning

confidence: 99%

Alternations in gut microbiota and host transcriptome of patients with coronary artery disease

Chen

Mou

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Coronary artery disease (CAD) is a widespread heart condition caused by atherosclerosis and influences millions of people worldwide. Early detection of CAD is challenging due to the lack of specific biomarkers. The gut microbiota and host-microbiota interactions have been well documented to affect human health. However, investigation that reveals the role of gut microbes in CAD is still limited. This study aims to uncover the synergistic effects of host genes and gut microbes associated with CAD through integrative genomic analyses. Results: Herein, we collected 54 fecal and 54 blood samples from CAD patients and matched controls, and performed amplicon and transcriptomic sequencing on these samples, respectively. By comparing CAD patients with health controls, we found that dysregulated gut microbes were significantly associated with CAD. By leveraging the Random Forest method, we found that 10 bacteria biomarkers can distinguish CAD patients from health controls with a high performance (AUC = 0.939). We observed that there existed prominent associations of gut microbes with several clinical indices relevant to heart functions. Integration analysis revealed that CAD-relevant gut microbe genus Fusicatenibacter was associated with expression of CAD-risk genes, such as GBP2, MLKL, and CPR65. In addition, the upregulation of immune-related pathways in CAD patients were identified to be primarily associated with higher abundance of genus Blautia, Eubacterium, Fusicatenibacter, and Monoglobus. Conclusions: Our results highlight that dysregulated gut microbes contribute risk to CAD by interacting with host genes. These identified microbes and interacted risk genes may have high potentials as biomarkers for CAD.

show abstract

Identification of MKNK1 and TOP3A as ovarian endometriosis risk-associated genes using integrative genomic analyses and functional experiments

Cited by 6 publications

References 62 publications

Variation of Structure and Cellular Functions of Type IA Topoisomerases across the Tree of Life

Variation of Structure and Cellular Functions of Type IA Topoisomerases across the Tree of Life

Alterations in gut microbiota and host transcriptome of patients with coronary artery disease

Alternations in gut microbiota and host transcriptome of patients with coronary artery disease

Contact Info

Product

Resources

About