<i>FAM13A</i> as a Novel Hypoxia-Induced Gene in Non-Small Cell Lung Cancer

Ziółkowska-Suchanek, Iwona; Mosor, Maria; Podralska, Marta; Iżykowska, Katarzyna; Gabryel, Piotr; Dyszkiewicz, Wojciech; Słomski, Ryszard; Nowak, Jerzy

doi:10.7150/jca.20342

Cited by 16 publications

(12 citation statements)

References 21 publications

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“…1), with the evolution of fully aquatic adults and viviparity . Among the genes identified on the T. compressicauda , the gene fam13a is involved in signal transduction (GO:0007165) and has been related to different lung diseases [71, 72] with its activity induced by low levels of O 2 [73]. While cutaneous gas exchange is important in Amphibia [74], T. compressicauda has the largest lungs of any caecilian [75], is reported to have more than 90% pulmonary oxygen uptake [76], and is able to tolerate hypoxic and hypercapnic conditions [77].…”

Section: Discussionmentioning

confidence: 99%

What lies beneath? Molecular evolution during the radiation of caecilian amphibians

et al. 2019

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Background Evolution leaves an imprint in species through genetic change. At the molecular level, evolutionary changes can be explored by studying ratios of nucleotide substitutions. The interplay among molecular evolution, derived phenotypes, and ecological ranges can provide insights into adaptive radiations. Caecilians (order Gymnophiona), probably the least known of the major lineages of vertebrates, are limbless tropical amphibians, with adults of most species burrowing in soils (fossoriality). This enigmatic order of amphibians are very distinct phenotypically from other extant amphibians and likely from the ancestor of Lissamphibia, but little to nothing is known about the molecular changes underpinning their radiation. We hypothesised that colonization of various depths of tropical soils and of freshwater habitats presented new ecological opportunities to caecilians. Results A total of 8540 candidate groups of orthologous genes from transcriptomic data of five species of caecilian amphibians and the genome of the frog Xenopus tropicalis were analysed in order to investigate the genetic machinery behind caecilian diversification . We found a total of 168 protein-coding genes with signatures of positive selection at different evolutionary times during the radiation of caecilians. The majority of these genes were related to functional elements of the cell membrane and extracellular matrix with expression in several different tissues. The first colonization of the tropical soils was connected to the largest number of protein-coding genes under positive selection in our analysis. From the results of our study, we highlighted molecular changes in genes involved in perception, reduction-oxidation processes, and aging that likely were involved in the adaptation to different soil strata. Conclusions The genes inferred to have been under positive selection provide valuable insights into caecilian evolution, potentially underpin adaptations of caecilians to their extreme environments, and contribute to a better understanding of fossorial adaptations and molecular evolution in vertebrates. Electronic supplementary material The online version of this article (10.1186/s12864-019-5694-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

What lies beneath? Molecular evolution during the radiation of caecilian amphibians

et al. 2019

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“…Gene expression analyses in cell lines from several tissues have demonstrated an increase in FAM13A levels in response to decrease in oxygen levels 34 . It has been suggested that lower oxygen tension might modulate FAM13A activity 35 , however, the exact mechanism has not been explained. In the COPD disease network module, AP3D1 (C AB gene) interacts with FAM13A and is an immediate neighbor of the CTGF gene, which is part of the hypoxia pathway (decrease in oxygen levels).…”

Section: Resultsmentioning

confidence: 99%

Integration of Molecular Interactome and Targeted Interaction Analysis to Identify a COPD Disease Network Module

Sharma

Kitsak

Cho

et al. 2018

Sci Rep

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The polygenic nature of complex diseases offers potential opportunities to utilize network-based approaches that leverage the comprehensive set of protein-protein interactions (the human interactome) to identify new genes of interest and relevant biological pathways. However, the incompleteness of the current human interactome prevents it from reaching its full potential to extract network-based knowledge from gene discovery efforts, such as genome-wide association studies, for complex diseases like chronic obstructive pulmonary disease (COPD). Here, we provide a framework that integrates the existing human interactome information with experimental protein-protein interaction data for FAM13A, one of the most highly associated genetic loci to COPD, to find a more comprehensive disease network module. We identified an initial disease network neighborhood by applying a random-walk method. Next, we developed a network-based closeness approach (CAB) that revealed 9 out of 96 FAM13A interacting partners identified by affinity purification assays were significantly close to the initial network neighborhood. Moreover, compared to a similar method (local radiality), the CAB approach predicts low-degree genes as potential candidates. The candidates identified by the network-based closeness approach were combined with the initial network neighborhood to build a comprehensive disease network module (163 genes) that was enriched with genes differentially expressed between controls and COPD subjects in alveolar macrophages, lung tissue, sputum, blood, and bronchial brushing datasets. Overall, we demonstrate an approach to find disease-related network components using new laboratory data to overcome incompleteness of the current interactome.

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“…In lung cancer, FAM13A was identified as a key regulator of tumor growth and progression [ 69 ]. In human lungs, FAM13A is expressed in airway epithelial and mucosal cells, club cells, alveolar type II epithelial cells and macrophages [ 68 ▪▪ , 70 ] and can be induced by hypoxia [ 72 ]. In COPD and IPF lung tissue, FAM13A expression was not influenced by allele carriage and was not significantly different from controls [ 46 , 49 ].…”

Section: Family With Sequence Similarity 13 Member Amentioning

confidence: 99%

Trade-offs in aging lung diseases

Moorsel

2018

Current Opinion in Pulmonary Medicine

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Purpose of reviewThe process of aging involves biological changes that increases susceptibility for disease. In the aging lung disease IPF, GWAS studies identified genes associated with risk for disease. Recently, several of these genes were also found to be involved in risk for COPD or lung cancer. This review describes GWAS-derived risk genes for IPF that overlap with risk genes for lung cancer or COPD.Recent findingsRisk genes that overlap between aging lung diseases, include FAM13A, DSP and TERT. Most interestingly, disease predisposing alleles for IPF are opposite to those for COPD or lung cancer. Studies show that the alleles are associated with differential gene expression and with physiological traits in the general population. The opposite allelic effect sizes suggest the presence of trade-offs in the aging lung. For TERT, the trade-off involves cellular senescence versus proliferation and repair. For FAM13A and DSP, trade-offs may involve protection from noxious gases or tissue integrity.SummaryThe overlap in risk genes in aging lung diseases provides evidence that processes associated with FAM13A, DSP and TERT are important for healthy aging. The opposite effect size of the disease risk alleles may represent trade-offs, for which a model involving an apicobasal gene expression gradient is presented.

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FAM13A as a Novel Hypoxia-Induced Gene in Non-Small Cell Lung Cancer

Cited by 16 publications

References 21 publications

What lies beneath? Molecular evolution during the radiation of caecilian amphibians

What lies beneath? Molecular evolution during the radiation of caecilian amphibians

Integration of Molecular Interactome and Targeted Interaction Analysis to Identify a COPD Disease Network Module

Trade-offs in aging lung diseases

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