Transcriptome Analysis on Monocytes from Patients with Neovascular Age-Related Macular Degeneration

Grunin, Michelle; Hagbi-Levi, Shira; Rinsky, Batya; Smith, Yoav; Chowers, Itay

doi:10.1038/srep29046

Cited by 35 publications

(28 citation statements)

References 74 publications

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“…Previous studies on TMEM176A mainly focused on its function in development and the immune system. [14][15][16] Tmem176a is highly expressed in retinoid-related orphan receptor gt (RORgt)C lymphocytes in mice. 17 Tmem176a induces the expression of co-stimulatory molecules, such as cluster of differentiation (CD)80, CD86, and CD40, and is involved in the maintenance of the immature state of dendritic cells in mice.…”

Section: Discussionmentioning

confidence: 99%

Methylation of TMEM176A is an independent prognostic marker and is involved in human colorectal cancer development

et al. 2017

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Colorectal cancer (CRC) is the third most common malignancy and the fourth most common cause of cancer related death worldwide. This study was designed to find tumor suppressors involved in CRC development by performing RNA-seq. Eight CRC cell lines and 130 cases of primary CRC samples were used. RNA-seq, methylation-specific PCR (MSP), flow cytometry, transwell assays, and a xenograft mouse model were used. Reduction of TMEM176A expression was confirmed in human CRC cells by RNA-seq. TMEM176A was expressed in LS180 and SW620 cells, loss of TMEM176A expression was observed in LOVO, HCT116, RKO, and DLD1 cells, and reduced TMEM176A expression was found in HT29 and SW480 cells. Unmethylation of the TMEM176A promoter was found in LS180 and SW620 cells, whereas complete methylation was found in LOVO, HCT116, RKO, and DLD1 cells, and partial methylation was found in HT29 and SW480 cells. Promoter region methylation correlated with loss of/reduced expression of TMEM176A. Re-expression of TMEM176A was induced by 5-aza-2'-deoxycytidine. TMEM176A was methylated in 50.77% of primary colorectal cancers. Methylation of TMEM176A was associated with tumor metastasis (P<0.05) and was an independent prognostic factor for 5-year overall survival (OS) according to Cox proportional hazards model analysis (P<0.05). TMEM176A induced apoptosis and inhibited cell migration and invasion in CRC cells. TMEM176A suppressed CRC cell growth both in vitro and in vivo. Our results suggest that expression of TMEM176A is regulated by promoter region methylation. TMEM176A methylation is an independent prognostic marker for 5-year OS in CRC, and may act as a tumor suppressor in CRC.

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Section: Discussionmentioning

confidence: 99%

Methylation of TMEM176A is an independent prognostic marker and is involved in human colorectal cancer development

et al. 2017

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“…whose Mos express the greatest amount of TNFα, have a higher prevalence of choroidal neovascularization (Cousins et al, 2004), and circulating blood Mo of patients with AMD express higher levels of CCL2, IL8, and VEGF (Lechner et al, 2017). The percentage of IL-6-expressing circulating Mos is higher in patients with neovascular AMD (Lechner et al, 2017) and these Mos more generally display an altered immune-related transcription signature (Grunin et al, 2016). Increased serum levels of IL-6 correlate with the incidence of ARM (Klein et al, 2014) and with late AMD (Klein et al, 2008a;Seddon et al, 2005).…”

Section: Mononuclear Phagocytes In Amdmentioning

confidence: 99%

On phagocytes and macular degeneration

Guillonneau

Eandi

Pâques

et al. 2017

Progress in Retinal and Eye Research

136

155

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Age related macular degeneration (AMD) is a complex multifactorial disease caused by the interplay of age and genetic and environmental risk factors. A common feature observed in early and both forms of late AMD is the breakdown of the physiologically immunosuppressive subretinal environment and the protracted accumulation of mononuclear phagocytes (MP). We here discuss the origin and nature of subretinal MPs, the mechanisms that lead to their accumulation, the inflammatory mediators they produce as well as the consequences of their chronic presence on photoreceptors, retinal pigment epithelium and choroid. Recent advances highlight how both genetic and environmental risk factors directly promote subretinal inflammation and tip the balance from a beneficial inflammation that helps control debris accumulation to detrimental chronic inflammation and destructive late AMD. Finally, we discuss how changes in life style or pharmacological intervention can help to break the vicious cycle of inflammation and degeneration, restore the immunosuppressive properties of the subretinal space, and reestablish homeostasis.

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“…35,37,38 Furthermore, based on selection of candidate proteins by proteomic analyses and subsequent targeted experiments, vinculin, phospholipid transfer protein (PLTP), and mannan-binding lectin serine protease 1 (MASP1) have been proposed as plasma biomarkers for AMD. 31,39 Besides proteins, miRNAs are interesting biomarker candidates for AMD, since AMD-specific miRNA profiles have been identified in plasma and serum.…”

Section: Age-related Macular Degeneration (Amd)mentioning

confidence: 99%

Omics Biomarkers in Ophthalmology

Jong

Lefeber

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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''Omics'' refers to high-throughput analyses of genes, proteins, or metabolites in a biological system, and is increasingly used for ophthalmic research. These system-based approaches can unravel disease-related processes and are valuable for biomarker discovery. Furthermore, potential therapeutic targets can be identified based on omics results, and targeted follow-up experiments can be designed to gain molecular understanding of the disease and to test new therapies. Here, we review the application of omics techniques in eye diseases, focusing on age-related macular degeneration (AMD), diabetic retinopathy (DR), retinal detachment (RD), myopia, glaucoma, Fuchs' corneal dystrophy (FCD), cataract, keratoconus, and dry eyes. We observe that genomic analyses were mainly successful in AMD research (almost half of the genomic heritability has been explained), whereas large parts of disease variability or risk remain unsolved in most of the other diseases. Other omics studies like transcriptomics, proteomics, and metabolomics provided additional candidate proteins and pathways for several eye diseases, although sample sizes in these studies were often very small and replication is lacking. In order to translate omics results into clinical biomarkers, larger sample sizes and validation across different cohorts would be essential. In conclusion, omicsbased studies are increasing in ophthalmology, and further application to the clinic might develop in the years to come. Integration of genomics with other type of omics data has the potential to improve the accuracy of predictive tests. Moreover, in the future, omics may lead to stratification of patients into subgroups based on molecular profiles, enabling the development of personalized treatments.

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Transcriptome Analysis on Monocytes from Patients with Neovascular Age-Related Macular Degeneration

Cited by 35 publications

References 74 publications

Methylation of TMEM176A is an independent prognostic marker and is involved in human colorectal cancer development

Methylation of TMEM176A is an independent prognostic marker and is involved in human colorectal cancer development

On phagocytes and macular degeneration

Omics Biomarkers in Ophthalmology

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