Estrogen receptors orchestrate cell growth and differentiation to facilitate liver regeneration

Kao, Ta Lun; Kuan, Yu Ping; Cheng, Wei‐Chung; Chang, Wei Chun; Jeng, Long Bin; Yeh, Shuyuan; Lung, Wen

doi:10.7150/thno.23624

Cited by 33 publications

(19 citation statements)

References 47 publications

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“…Among these, IFNA5 deletion (5.09% of LGG samples), IFNA8 deletion (5.28% of LGG samples), and DTX3 amplification (3.52% of LGG samples) indicated poor survival in LGG. Kao et al (2018) found that the upregulation of IFNA5 activated the ERβ-Ube3a interaction which further facilitated hepatic progenitor cell differentiation. Human epidemiologic studies showed that SNPs in IFNA8 were significantly associated with the overall survival of patients with WHO grade 2 to 3 gliomas ( Fujita et al, 2010 ).…”

Section: Discussionmentioning

confidence: 96%

Identifying Key Somatic Copy Number Alterations Driving Dysregulation of Cancer Hallmarks in Lower-Grade Glioma

et al. 2021

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Somatic copy-number alterations (SCNAs) are major contributors to cancer development that are pervasive and highly heterogeneous in human cancers. However, the driver roles of SCNAs in cancer are insufficiently characterized. We combined network propagation and linear regression models to design an integrative strategy to identify driver SCNAs and dissect the functional roles of SCNAs by integrating profiles of copy number and gene expression in lower-grade glioma (LGG). We applied our strategy to 511 LGG patients and identified 98 driver genes that dysregulated 29 cancer hallmark signatures, forming 143 active gene-hallmark pairs. We found that these active gene-hallmark pairs could stratify LGG patients into four subtypes with significantly different survival times. The two new subtypes with similar poorest prognoses were driven by two different gene sets (one including EGFR, CDKN2A, CDKN2B, INFA8, and INFA5, and the other including CDK4, AVIL, and DTX3), respectively. The SCNAs of the two gene sets could disorder the same cancer hallmark signature in a mutually exclusive manner (including E2F_TARGETS and G2M_CHECKPOINT). Compared with previous methods, our strategy could not only capture the known cancer genes and directly dissect the functional roles of their SCNAs in LGG, but also discover the functions of new driver genes in LGG, such as IFNA5, IFNA8, and DTX3. Additionally, our method can be applied to a variety of cancer types to explore the pathogenesis of driver SCNAs and improve the treatment and diagnosis of cancer.

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Section: Discussionmentioning

confidence: 96%

Identifying Key Somatic Copy Number Alterations Driving Dysregulation of Cancer Hallmarks in Lower-Grade Glioma

et al. 2021

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“…These mechanisms include DNA fragmentation (27), TP53 signaling enhancement (28), JNK pathway amplification (29), and cellular differentiation (20,30). Also, Kao et al have shown that ERβ-UBE3A interaction promotes liver cell differentiation while ERα facilitates proliferation (31). However, a previous study showed that without estrogen, MG132 failed to increase basal ERβ-mediated transcription in 293T cells (32).…”

Section: Discussionmentioning

confidence: 99%

N-myc downstream-regulated gene 2 promotes the protein stability of estrogen receptor beta via inhibition of ubiquitin-protein ligase E3A to suppress colorectal cancer

Jun¹,

Lv²,

Hao³

et al. 2020

J Gastrointest Oncol

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Background: N-myc downstream-regulated gene 2 (NDRG2) and estrogen receptor beta (ERβ) both play key roles in cellular differentiation in colorectal cancer (CRC). Previous studies have demonstrated that ERβ co-locates with and directly transactivates NDRG2. However, the effect of NDRG2 on ERβ and its underlying mechanism remain largely unknown. Our aim of the study is to explore the effect of NDRG2 on ERβ and their contributions to progression of CRC. Methods: The Cancer Genome Atlas (TCGA) database was first utilized to validate the clinical significance of ERβ and NDRG2 in CRC. MTT and scratch migration assays were carried out to verify the role of ERβ and NDRG2 in CRC cells. Western blotting and polymerase chain reaction were performed to analyze the effect of NDRG2 on ERβ, and an immunoprecipitation assay was conducted to explore the protein-protein interaction.Results: ERβ and NDRG2 were both found to be significantly down-regulated in tumor tissues from the TCGA-CRC database. NDRG2 was also observed to enhance the protein stability of ERβ while could not change messenger RNA (mRNA) level of ESR2 (encoding ERβ). A positive relationship was found to exist between the two proteins in CRC cells, with NDRG2 prolonging the half-life of ERβ and improving its nuclear translocation. Through detecting expression of ERβ downstream genes (such as TP53 and JNK) and performing related function experiment, we demonstrated that NDRG2 could promote transcriptional activation of ERβ target genes and enhance the function of tumor suppressors when the ERβ agonist diarylpropionitrile (DPN). The immunoprecipitation assay showed that NDRG2 could affect the complex components of ubiquitin-protein ligase E3A (UBE3A, known as E6AP) and ERβ, reducing the ubiquitinmediated proteasome degradation of ERβ. Conclusions: In the current study, we found that NDRG2 could bind with UBE3A to hinder the binding of UBE3A with ERβ. Moreover, a positive feedback loop was discovered between NDRG2 and ERβ, which

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“…The ERα-knockout (KO) mice ( ActbCre-ERα loxP/loxP ) and ERβ-KO mice ( ERβ –/– ) used in our study were kindly provided by Prof. Shuyuan Yeh and Prof. Chawnshang Chang, respectively, at the University of Rochester, NY, USA ( 31 , 32 ). To generate ERα-KO mice ( 33 , 34 ), transgenic ERα loxP/loxP mice were crossed with ActbCre (β-actin promoter–driven Cre recombinase) transgenic mice to generate male ERα-KO ( ERα –/– ) mice. The control mice were ERα loxP/loxP without ActbCre .…”

Section: Methodsmentioning

confidence: 99%

Add-On Selective Estrogen Receptor Modulators for Methadone Maintenance Treatment

et al. 2021

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Methadone maintenance treatment (MMT) remains the cornerstone for the management of opiate abuse. However, MMT can be associated with complex factors, including complications during the tolerance phase, the inability of some patients to maintain treatment effects during the tapering or abstinence phases, and the development of methadone dependence. Previous studies have revealed a sex disparity in MMT efficacy, showing that women undergoing MMT experiencing an increase in psychological symptoms compared with men and suggesting a link between disparate responses and the effects of estrogen signaling on methadone metabolism. More specifically, estradiol levels are positively associated with MMT dosing, and the expression of a single-nucleotide polymorphism (SNP) associated with estrogen receptor (ER) regulation is also associated with MMT dosing. In addition to performing mechanistic dissections of estrogen signaling in the presence of methadone, past studies have also proposed the targeting of estrogen signaling during MMT. The present report provides an overview of the relevant literature regarding sex effects, including differences in sex hormones and their potential impacts on MMT regimens. Moreover, this article provides a pharmacological perspective on the targeting of estrogen signals through the use of selective ER modulators (SERMs) during MMT. Preliminary preclinical experiments were also performed to evaluate the potential effects of targeting estrogen signaling with tamoxifen on methadone metabolism.

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Estrogen receptors orchestrate cell growth and differentiation to facilitate liver regeneration

Cited by 33 publications

References 47 publications

Identifying Key Somatic Copy Number Alterations Driving Dysregulation of Cancer Hallmarks in Lower-Grade Glioma

Identifying Key Somatic Copy Number Alterations Driving Dysregulation of Cancer Hallmarks in Lower-Grade Glioma

N-myc downstream-regulated gene 2 promotes the protein stability of estrogen receptor beta via inhibition of ubiquitin-protein ligase E3A to suppress colorectal cancer

Add-On Selective Estrogen Receptor Modulators for Methadone Maintenance Treatment

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