Growth Hormone Receptor Regulation in Cancer and Chronic Diseases

Strous, Ger J.; Almeida, Ana Da Silva; Putters, Joyce; Schantl, Julia; Sedek, Magdalena; Slotman, Johan A.; Nespital, Tobias; Hassink, Gerrit Cornelis; Mol, Jan A.

doi:10.3389/fendo.2020.597573

Cited by 42 publications

(37 citation statements)

References 339 publications

(408 reference statements)

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“…acromegaly. Growth hormone signalling is further related to metabolic alterations and some cancers 60 . A similar principle could be relevant to other growth or regulatory factors.…”

Section: Discussionmentioning

confidence: 99%

GWAS of allometric body-shape indices in UK Biobank identifies loci suggesting associations with morphogenesis, organogenesis, adrenal cell renewal and cancer

Christakoudi

Εvangelou

Riboli

et al. 2021

Sci Rep

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Genetic studies have examined body-shape measures adjusted for body mass index (BMI), while allometric indices are additionally adjusted for height. We performed the first genome-wide association study of A Body Shape Index (ABSI), Hip Index (HI) and the new Waist-to-Hip Index and compared these with traditional indices, using data from the UK Biobank Resource for 219,872 women and 186,825 men with white British ancestry and Bayesian linear mixed-models (BOLT-LMM). One to two thirds of the loci identified for allometric body-shape indices were novel. Most prominent was rs72959041 variant in RSPO3 gene, expressed in visceral adipose tissue and regulating adrenal cell renewal. Highly ranked were genes related to morphogenesis and organogenesis, previously additionally linked to cancer development and progression. Genetic associations were fewer in men compared to women. Prominent region-specific associations showed variants in loci VEGFA and HMGA1 for ABSI and KLF14 for HI in women, and C5orf67 and HOXC4/5 for ABSI and RSPO3, VEGFA and SLC30A10 for HI in men. Although more variants were associated with waist and hip circumference adjusted for BMI compared to ABSI and HI, associations with height had previously been reported for many of the additional variants, illustrating the importance of adjusting correctly for height.

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“…acromegaly. Growth hormone signalling is further related to metabolic alterations and some cancers 60 . A similar principle could be relevant to other growth or regulatory factors.…”

Section: Discussionmentioning

confidence: 99%

GWAS of allometric body-shape indices in UK Biobank identifies loci suggesting associations with morphogenesis, organogenesis, adrenal cell renewal and cancer

Christakoudi

Εvangelou

Riboli

et al. 2021

Sci Rep

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“…This process can stimulate the response of the innate immune system (47). GO enrichment analysis has shown that 380 genes across host clusters were enriched with functions which play essential roles in mediating cellular entry of pathogens ( e.g ., epidermal growth factor receptor (EGFR) signalling pathway (48), growth hormone receptor signalling pathway (49), mitochondrial ATP synthesis coupled electron transport (50), protein targeting to endoplasmic reticulum(51)), communication of bacteria with the host environment ( e.g ., positive regulation of establishment of protein localization(52)), control of infection ( e.g ., regulation of protein metabolic process(53)), invading pathogen ( e.g ., response to laminar fluid shear stress (54)), and co-opting host factors ( e.g ., viral gene expression (55)) that can be considered as potential targets in designing antibacterial therapies. Enriched functions were mostly observed at 24h and 4h pi in the host and pathogen, respectively, with mainly downregulated expression (Supplementary Table).…”

Section: Resultsmentioning

confidence: 99%

dSeqSb: A systems biology approach to decipher dynamics of host-pathogen interactions using temporal dual RNA-seq data

Dinarvand

Koch

Mouiee

et al. 2022

Preprint

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Infection triggers a dynamic cascade of reciprocal events between host and pathogen wherein the host activates complex mechanisms to recognise and kill pathogens while the pathogen adjusts its virulence and fitness to avoid eradication by the host. The interaction between the pathogen and the host results in large-scale changes in gene expression in both organisms. Dual RNA-seq, the simultaneous detection of host and pathogen transcripts, has become a leading approach to unravel complex molecular interactions between the host and the pathogen and is particularly informative for intracellular organisms. The amount of in vitro and in vivo dual RNA-seq data is rapidly growing which demands computational pipelines to effectively analyse such data. In particular, holistic, systems-level, and temporal analyses of dual RNA-seq data are essential to enable further insights into the host-pathogen transcriptional dynamics and potential interactions. Here, we developed an integrative network-driven bioinformatics pipeline, dRNASb, a systems biology-based computational pipeline to analyse temporal transcriptional clusters, incorporate molecular interaction networks (e.g., protein-protein interactions), identify topologically and functionally key transcripts in host and pathogen, and associate host and pathogen temporal transcriptome to decipher potential between-species interactions. The pipeline is applicable to various dual RNA-seq data from different species and experimental conditions. As a case study, we applied dRNASb to analyse temporal dual RNA-seq data of Salmonella-infected human cells, which enabled us to uncover genes contributing to the infection process and their potential functions and to identify potential host-pathogen interactions between host and pathogen genes. Overall, dRNASb has the potential to identify key genes involved in bacterial growth or host defence mechanisms for future uses as therapeutic targets.

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“…We find strong colocalization of this locus with distal-eQTLs of CSH1 with PP.H4 = 0.913 ( Figure 4B ). CSH1 codes for a somatotropin hormone, belonging to a family of hormones with paracrine signaling functions promoting cell division and growth in glands 88 . Using non-cancerous breast tissue eQTLs, we find strong colocalization with overall breast cancer risk with local-eQTLs of RUSC1-AS1 and distal-eQTLs of SH2B1 ( Figure 4C ).…”

Section: Resultsmentioning

confidence: 99%

Section: Mediated Distal-eqtl Signal In Breast and Prostate Overlaps ...mentioning

confidence: 99%

Distal gene regulation mediated by non-coding RNAs contributes to germline risk for breast and prostate cancer

Cole

Lee

Schwarz

et al. 2022

Preprint

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Genome-wide association studies (GWAS) have identified numerous genetic loci associated with breast and prostate cancer risk, suggesting that germline genetic dysregulation influences tumorigenesis. However, the biological function underlying many genetic associations is not well-understood. Previous efforts to annotate loci focused on protein-coding genes (pcGenes) largely ignore non-coding RNAs (ncRNAs) which account for most transcriptional output in human cells and can regulate transcription of both pcGenes and other ncRNAs. Though the biological roles of most ncRNAs are not well-defined, many ncRNAs are involved in cancer development. Here, we explore one regulatory hypothesis: ncRNAs as trans-acting mediators of gene expression regulation in non-cancerous and tumor breast and prostate tissue. Using germline genetics as a causal anchor, we categorize distal (>1 Megabase) expression quantitative trait loci (eQTLs) of pcGenes significantly mediated by local-eQTLs of ncRNAs (within 1 Megabase). We find over 300 mediating ncRNAs and show the linked pcGenes are enriched for immunoregulatory and cellular organization pathways. By integrating eQTL and cancer GWAS results through colocalization and genetically-regulated expression analyses, we detect overlapping signals in nine known breast cancer loci and one known prostate cancer locus, and multiple novel genetic associations. Our results suggest a strong transcriptional impact of ncRNAs in breast and prostate tissue with implications for cancer etiology. More broadly, our framework can be systematically applied to functional genomic features to characterize genetic variants distally-regulating transcription through trans-mechanisms.

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Growth Hormone Receptor Regulation in Cancer and Chronic Diseases

Cited by 42 publications

References 339 publications

GWAS of allometric body-shape indices in UK Biobank identifies loci suggesting associations with morphogenesis, organogenesis, adrenal cell renewal and cancer

GWAS of allometric body-shape indices in UK Biobank identifies loci suggesting associations with morphogenesis, organogenesis, adrenal cell renewal and cancer

dSeqSb: A systems biology approach to decipher dynamics of host-pathogen interactions using temporal dual RNA-seq data

Distal gene regulation mediated by non-coding RNAs contributes to germline risk for breast and prostate cancer

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