Estrogen Promotes cAMP Production in Mesenchymal Stem Cells by Regulating ADCY2

Zhao, Guangfeng; Li, Xiujun; Miao, Huishuang; Chen, Shiwen; Hou, Yayi

doi:10.15283/ijsc19139

Cited by 11 publications

(13 citation statements)

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“…The latter is a crucial signal in cell fate, inflammation, and many other bioactivities, and is also greatly involved in the growth and differentiation of MSCs. (39). In colorectal cancer, ADCY2 could also be an important prognostic marker (40).…”

Section: Discussionmentioning

confidence: 99%

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A Novel Lipid Prognostic Signature of ADCY2, LIPE, and OLR1 in Head and Neck Squamous Cell Carcinoma

et al. 2021

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Simple SummaryClinically, aberrant lipid metabolism is responsible for overweight and/or obesity. Overweight is considered as an independent factor of cancer risk in 2019. Therefore, lipid metabolic reprogramming is an emerging hallmark of malignancy. It is an urgent need to comprehensively understand the relationship among lipid metabolism and HNSCC and identify a valuable biomarker for predicting prognosis of HNSCC patients. Three new findings were found in this study. Firstly, we identified the lipid-related differentially expressed genes (DEGs) by using the GEO microarrays and TCGA dataset. A novel lipid-related mRNA prognostic signature (LRPS, consisting of ADCY2, LIPE and OLR1) was developed, which could predict the survival and prognosis of HNSCC patients as an independent effective prognostic factor. Secondly, we found that the LRPS could indicate the type of infiltrated immune cells in HNSCC tumor microenvironment. Thirdly, we verified that the LPPS score could interpret the TP53 status of HNSCC. Our new findings indicated that LRPS has a potential to be a promising indicator of overall survival, TP53 status, and immune characteristics in HNSCC, and perhaps can monitor and guide the treatment efficacy and prognosis of HNSCC in the future.BackgroundHead and neck squamous cell carcinoma (HNSCC) is characterized by a high frequency of lymph node metastasis and a high mortality. Lipid metabolic reprogramming is an emerging carcinogen as its role in fulfilling cancer growth and spread. However, little is known about the correlation between lipid metabolism and HNSCC.Materials and MethodsExpressions of lipid-related genes were obtained from the Cancer Genome Atlas (TCGA) and Gene expression Omnibus (GEO) databases for differential and functional analyses. A total number of 498 patients from TCGA with complete information were included to identify a lipid-related prognostic signature (LRPS), based on ADCY2, LIPE, and OLR1, by using univariate and multivariate Cox regression analyses. LRPS-high and LRPS-low groups were accordingly divided to pathway and cell enrichment analyses.ResultsLRS-low patients had a better overall survival and relapse - free survival than LRS-high ones in HNSCC. The LRPS-high group was significantly related to perineural invasion of cancer, cancer-related pathways, high TP53 mutation rate, high proportion of natural killer T cells (NKT), dendritic cells, monocytes, Treg, and M1 and M2 macrophage infiltration in HNSCC tumor tissues. Conversely, the LRPS-low group correlated with DNA damage-related and T-cell-regulated pathways, low frequency of mutated TP53, and high infiltration of B cells and CD4+ effector cells including Th1 and Th2.ConclusionLRPS has a potential to be a promising indicator of overall survival, prognosis, TP53 status, and immune characteristics in HNSCC.

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Section: Discussionmentioning

confidence: 99%

“…Zhao et al. have reported E2-induced ADCY2 as a positive regulator in MSCs ( 39 ). In colorectal cancer, ADCY2 could also be an important prognostic marker ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

A Novel Lipid Prognostic Signature of ADCY2, LIPE, and OLR1 in Head and Neck Squamous Cell Carcinoma

et al. 2021

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“…In addition to this, a gene whose expression is known to be greatly upregulated in the presence of estradiol, ADCY2, was a candidate gene in the current study. This regulation is mediated by interactions between estradiol and miRNA's that bind to the 3'UTR of ADCY2 (Zhao et al, 2020). The motif analysis presented here found that there are 40 transcription factors predicted to bind to the unique parapatricM.…”

Section: Functional Characterization Of Variants and Motif Analysismentioning

confidence: 71%

Genomic analysis of the rhesus macaque (Macaca mulatta) and the cynomolgus macaque (Macaca fascicularis) uncover polygenic signatures of reinforcement speciation

Bailey

Ruiz

Tosi

et al. 2023

Preprint

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Speciation can be caused by divergent adaptation in allopatry as a result of ecological or reproductive character displacement in sympatry or parapatry. The latter can result as a means of preventing hybridization, a process known as reinforcement speciation. Though this has been described in a variety of taxonomic systems though the prevalence throughout nature is still unknown. In this study, we use whole-genome sequencing (WGS) of two primate species that have experienced introgression in their history, the rhesus (Macaca mulatta) and cynomolgus (M. fascicularis) macaques, to identify genes exhibiting a pattern of reproductive character displacement consistent with reinforcement speciation. Using windowed scans of various population genetic statistics to identify reproductive character displacement, we find candidate genes associated with a variety of functions, including an overrepresentation of multiple neurological functions and some genes involved in sexual development and gametogenesis. This suggests a variety of genes acting at multiple stages of a reinforcement process between these species. We also find signatures of introgression of the Y-chromosome that confirm previous studies suggesting male-driven introgression of M. mulatta into M. fascicularis populations. This study is among the first to utilize whole-genome sequencing to analyze the phenomenon of reinforcement and among the first to find evidence of this phenomenon in primates, particularly ones that have medical relevance.

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“…When investigating PFOA + ZAL-upregulated genes at D50, we noted the presence of one important gene-Adcy2-in multiple signaling pathways. It was reported that estradiol upregulates Adcy2 and, subsequently, promotes the production of cAMP in mesenchymal stem cells [54]. Adcy2 encodes a member of the adenylyl cyclase family, which catalyzes the conversion of ATP to cAMP.…”

Section: Discussionmentioning

confidence: 99%

Effects of Pubertal Exposure to Butyl Benzyl Phthalate, Perfluorooctanoic Acid, and Zeranol on Mammary Gland Development and Tumorigenesis in Rats

Santucci-Pereira

Dang

et al. 2022

IJMS

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Endocrine-disrupting chemicals (EDCs)—including butyl benzyl phthalate (BBP), perfluorooctanoic acid (PFOA), and zeranol (α-ZAL, referred to as ZAL hereafter)—can interfere with the endocrine system and produce adverse effects. It remains unclear whether pubertal exposure to low doses of BBP, PFOA, and ZAL has an impact on breast development and tumorigenesis. We exposed female Sprague Dawley rats to BBP, PFOA, or ZAL through gavage for 21 days, starting on day 21, and analyzed their endocrine organs, serum hormones, mammary glands, and transcriptomic profiles of the mammary glands at days 50 and 100. We also conducted a tumorigenesis study for rats treated with PFOA and ZAL using a 7,12-dimethylbenz[a]anthracene (DMBA) model. Our results demonstrated that pubertal exposure to BBP, PFOA, and ZAL affected endocrine organs and serum hormones, and induced phenotypic and transcriptomic changes. The exposure to PFOA + ZAL induced the most phenotypic and transcriptomic changes in the mammary gland. PFOA + ZAL downregulated the expression of genes related to development at day 50, whereas it upregulated genes associated with tumorigenesis at day 100. PFOA + ZAL exposure also decreased rat mammary tumor latency, reduced the overall survival of rats after DMBA challenge, and affected the histopathology of mammary tumors. Therefore, our study suggests that exposure to low doses of EDCs during the pubertal period could induce changes in the endocrine system and mammary gland development in rats. The inhibition of mammary gland development by PFOA + ZAL might increase the risk of developing mammary tumors through activation of signaling pathways associated with tumorigenesis.

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Estrogen Promotes cAMP Production in Mesenchymal Stem Cells by Regulating ADCY2

Cited by 11 publications

References 37 publications

A Novel Lipid Prognostic Signature of ADCY2, LIPE, and OLR1 in Head and Neck Squamous Cell Carcinoma

A Novel Lipid Prognostic Signature of ADCY2, LIPE, and OLR1 in Head and Neck Squamous Cell Carcinoma

Genomic analysis of the rhesus macaque (Macaca mulatta) and the cynomolgus macaque (Macaca fascicularis) uncover polygenic signatures of reinforcement speciation

Effects of Pubertal Exposure to Butyl Benzyl Phthalate, Perfluorooctanoic Acid, and Zeranol on Mammary Gland Development and Tumorigenesis in Rats

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