Steroidogenic Factor 1 (NR5A1) Activates ATF3 Transcriptional Activity

Emura, Natsuko; Wang, Chiung-Min; Yang, William H.; Yang, Wei‐Hsiung

doi:10.3390/ijms21041429

Cited by 3 publications

(2 citation statements)

References 44 publications

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“…A study of Hill et al demonstrated that DDC-induced chronic inflammation could prompt rapid progression of intrahepatic cholangiocarcinoma [43]. NR5A1 is an orphan nuclear receptor which is proved to be essential for sexual differentiation and development of multiple endocrine organs, as well as the proliferation of cancer cells [44]. Evidences have shown that PDCD4 plays a critical role in the progression of several tumors [45][46][47], and serves as a tumor suppressor in PCa to modulate tumor growth and castration resistance [48].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic implications for localized prostate cancer by multiomics analyses of the ageing microenvironment landscape

Gui¹,

Wei²,

Mo³

et al. 2023

Int. J. Biol. Sci.

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Background: Numerous studies have substantiated the association between aging and the progression of malignant tumors in humans, notably prostate cancer (PCa). Nevertheless, to the best of our knowledge, no studies have comprehensively elucidated the intricate characteristics of the aging microenvironment (AME) in PCa. Methods: AME regulatory patterns were determined using the NMF algorithm. Then an ageing microenvironment index (AMI) was constructed, with excellent prognostic and immunotherapy prediction ability, and its' clinical relevance was surveyed through spatial transcriptomics. Further, the drug response was analysed using the Genomics of Drug Sensitivity in Cancer (GDSC), the Connectivity Map (CMap) and CellMiner database for patients with PCa. Finally, the AME was studied using in vitro and vivo experiments. Results: Three different AME regulatory patterns were identified across 813 PCa patients, associated with distinct clinical prognosis and physiological pathways. Based on the AMI, patients with PCa were divided into the high-score and low-score subsets. Higher AMI score was significantly infiltrated with more immune cells, higher rate of biochemical recurrence (BCR) and worse response to immunotherapy, antiandrogen therapy and chemotherapy in PCa. In addition, we found that the combination of bicalutamide and embelin was capable of suppressing tumor growth of PCa. Besides, as the main components of AMI, COL1A1 and BGLAP act as oncogenes and were verified via in vivo and in vitro experiments. Conclusions: AME regulation is significantly associated with the diversity and complexity of TME. Quantitative evaluation of the AME regulatory patterns may provide promising novel molecular markers for individualised therapy in PCa.

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Section: Discussionmentioning

confidence: 99%

Therapeutic implications for localized prostate cancer by multiomics analyses of the ageing microenvironment landscape

Gui¹,

Wei²,

Mo³

et al. 2023

Int. J. Biol. Sci.

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“…The steroidogenic factor-1 (SF-1) gene is an orphan nuclear receptor encoded by the Ftz-Fl gene, which is one kind of the atypical nuclear receptor [4]. As the main regulator of cholesterol metabolism, SF-1 can activate the cholesterol migration and the expression of genes related to adrenal steroidogenesis and plays an important role in the biosynthesis and development of steroid hormones [5,6].…”

Section: Introductionmentioning

confidence: 99%

Abnormal Methylation of SF-1 Gene Promoter Region in Endometrial Cancer and Its Mechanism

Huang

Jia

Jiang

et al. 2021

Preprint

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We aim to investigate the methylation status, protein expression and clinical significance of the steroidogenic factor-1(SF-1) in endometrial carcinoma (EC), and explore the effect of abnormal methylation of SF-1 on the biological behaviour of EC. Bisulfite sequencing (BSP), western blotting (WB), and immunohistochemical were used to detect the methylation status and protein expression of SF-1 in EC tissues, paracancerous tissues and normal endometrial tissues. DNA methyltransferase inhibitor 5-Aza-CdR were used to treat HEC-1-A cell lines to demethylate SF-1. After treatment, WB and qPCR were used to detect the expression of SF-1 and its downstream target genes. Cell proliferation and apoptosis were detected by the EdU fluorescent labelling method and flow cytometry between the groups. Compared with paracancerous tissues and normal endometrial tissues, the expression of SF-1 protein in EC tissues was significantly increased (P﹤0.05). The percentage of methylated cytosine in the promoter region of the SF-1 gene in EC tissues (8.2%) was significantly lower than that in paracancerous tissues by 40.9% (P<0.05). Compared with the control group, after 5-Aza-CdR treatment, the methylation level of the SF-1 gene was significantly reduced (P﹤0.05), the expressions of SF-1 and its downstream target genes were significantly increased (P <0.05), the cell proliferation was enhanced and the cell apoptosis was significantly reduced (P <0.05). In conclusion, in EC, SF-1 gene was hypomethylated and the expression of SF-1 was increased, which promotes cell proliferation and inhibits cell apoptosis. SF-1 may become a new molecular target for early diagnosis and treatment in EC.

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An organotypic atlas of human vascular cells

Barnett,

Cujba,

Yang

et al. 2024

Nat Med

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The human vascular system, comprising endothelial cells (ECs) and mural cells, covers a vast surface area in the body, providing a critical interface between blood and tissue environments. Functional differences exist across specific vascular beds, but their molecular determinants across tissues remain largely unknown. In this study, we integrated single-cell transcriptomics data from 19 human organs and tissues and defined 42 vascular cell states from approximately 67,000 cells (62 donors), including angiotypic transitional signatures along the arterial endothelial axis from large to small caliber vessels. We also characterized organotypic populations, including splenic littoral and blood–brain barrier ECs, thus clarifying the molecular profiles of these important cell states. Interrogating endothelial–mural cell molecular crosstalk revealed angiotypic and organotypic communication pathways related to Notch, Wnt, retinoic acid, prostaglandin and cell adhesion signaling. Transcription factor network analysis revealed differential regulation of downstream target genes in tissue-specific modules, such as those of FOXF1 across multiple lung vascular subpopulations. Additionally, we make mechanistic inferences of vascular drug targets within different vascular beds. This open-access resource enhances our understanding of angiodiversity and organotypic molecular signatures in human vascular cells, and has therapeutic implications for vascular diseases across tissues.

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Steroidogenic Factor 1 (NR5A1) Activates ATF3 Transcriptional Activity

Cited by 3 publications

References 44 publications

Therapeutic implications for localized prostate cancer by multiomics analyses of the ageing microenvironment landscape

Therapeutic implications for localized prostate cancer by multiomics analyses of the ageing microenvironment landscape

Abnormal Methylation of SF-1 Gene Promoter Region in Endometrial Cancer and Its Mechanism

An organotypic atlas of human vascular cells

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