Abstract 2431: EFNA3, a key functional mediator of hypoxic microenvironment in hepatocellular carcinoma

Husain, Abdullah; Chiu, Yung Tuen; Ho, Danny; Sze, Karen Man Fong; Chan, Lo Kong; Tsui, Yu Man; Wong, Carmen Chak‐Lui; Ng, Irene Oi Lin

doi:10.1158/1538-7445.am2018-2431

Cited by 3 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The candidate gene igf1ra, identified in this study, codes for IGF-1 receptor-a, a receptor of insulin-like growth factor that was reported to be a primary mediator of growth hormones [38]. The ephrin-A3 gene (efna3) is shown as a key functional mediator of hypoxic microenvironment and is regarded as a therapeutic target for hypoxia-specific disease [39]. Retinoic acid receptor-related orphan receptor alpha (rora) was demonstrated to be an important mediator of HIF-1α activities in human [40].…”

Section: Discussionmentioning

confidence: 88%

Genome-wide Association Analysis of Adaptation to Oxygen Stress in Nile Tilapia (Oreochromis Niloticus)

Megens

Mengistu

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Tilapia is one of the most abundant species in aquaculture. Hypoxia is known to depress growth rate, but the genetic mechanism by which this occurs is unknown. In this study, two groups consisting of 3140 fish that were raised in either aerated (normoxia) or non-aerated pond (nocturnal hypoxia). During grow out, fish were sampled five times to determine individual body weight (BW) gains. We applied a genome-wide association study to identify SNPs and genes associated with the hypoxic and normoxic environments in the 17th generation of a Genetically Improved Farmed tilapia population. Results: In the hypoxic environment, 36 SNPs associated with at least one of the five body weight measurements (BW1 till BW5), of which six, located between 19.48 Mb and 21.04 Mb on Linkage group (LG) 8, were significant for body weight in the early growth stage (BW1 to BW2). Further significant associations were found for BW in the later growth stage (BW3 to BW5), located on LG1 and LG8. Analysis of genes within the candidate genomic region suggested that MAPK and VEGF signalling were significantly involved in the later growth stage under the hypoxic environment. Well-known hypoxia-regulated genes such as igf1rb, rora, efna3 and aurk were also associated with growth in the later stage in the hypoxic environment. Conversely, 13 linkage groups containing 29 unique significant and suggestive SNPs were found across the whole growth period under the normoxic environment. A meta-analysis showed that 33 SNPs were significantly associated with BW across the two environments, indicating a shared effect independent of hypoxic or normoxic environment. Functional pathways involved in nervous system development and organ growth in the early stage, and oocyte maturation in the later stage.Conclusions: There are clear genotype-growth associations in both normoxic and hypoxic environments, although genome architecture involved changed over the growing period, indicating a transition in metabolism along the way. The involvement of pathways important in hypoxia especially at the later growth stage indicates a genotype-by-environment interaction, in which MAPK and VEGF signalling are important components.

show abstract

Section: Discussionmentioning

confidence: 88%

Genome-wide Association Analysis of Adaptation to Oxygen Stress in Nile Tilapia (Oreochromis Niloticus)

Megens

Mengistu

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The candidate gene igf1ra, identified in this study, codes for IGF-1 receptor-a, a receptor of insulin-like growth factor that was reported to be a primary mediator of growth hormones [37]. The ephrin-A3 gene (efna3) is shown as a key functional mediator of hypoxic microenvironment and is regarded as a therapeutic target for hypoxia-specific disease [38]. Retinoic acid receptor-related orphan receptor alpha (rora) was demonstrated to be a key regulator of HIF-1α activities in human [39].…”

Section: Discussionmentioning

confidence: 88%

Genomic architecture of selection for adaptation to challenging environments in aquaculture

Yu¹

View full text Add to dashboard Cite

Yu, X. (2022). Genomic architecture of selection for adaptation to challenging environments in Aquaculture. PhD thesis, Wageningen University and Research, the Netherlands.Aquaculture, including freshwater and marine farming, has been important for global fish production during the past few decades. However, climate change presents a major risk threatening both quality and quantity of aquaculture production. The environmental stressors in aquaculture resulting from climate change, are temperature rise, salinity changes, sea level rise, acidification and changes of other chemical properties and changes of oxygen levels. Although a reasonable genetic gain can be achieved by selective breeding, this genetic response may not be enough to adapt fish species to the effects of climate change. Markerassisted selection focusing on specific genes or alleles that allow fish to cope with these changes would allow more rapid adaptation of fish to these new environments. In this thesis, I focused on three essential environmental stressorsdissolved oxygen, salinity and temperature as primarily determined in aquaculture production. The main objective is to provide insight in the genomic architecture underlying the mechanism of adaptation to challenging environments of aquaculture species under farming conditions. First, I determined candidate QTL associated with phenotypic variation during adaptation to hypoxia or normoxia. I identified overrepresented pathways that could explain the genetic regulation of hypoxia on growth. To identify fish with better hypoxia tolerance and growth under a hypoxic environment, I quantified the genetic correlations between an indicator trait for hypoxia tolerance (critical swimming performance) and growth. Moreover, the genomic architecture associated with swimming performance was demonstrated, while the effect of significant QTLs on growth was estimated. Beyond applying genome-wide association studies, I used selection signatures to identify QTLs and genes contributing to salinity tolerance. In addition, I also compared the genome of the saline-tolerant and highly productive tilapia "Sukamandi", that was developed by the aquaculture research institute in Indonesia, to that of blue tilapia and Nile tilapia, to identify the QTLs contributing to salinity tolerance. Finally, I investigated QTLs associated with growth-related traits and organ weights at two distinct commercial Mediterranean product sites differing in temperature (farms in Spain and Greece). Overall, this thesis considerably adds to insight into how fish adapt to challenging environments, which will aid marker-assisted selection for improved resilience of aquaculture species under climate change. ContentsChapter 1 General introductionChapter 2 Genome-wide association analysis of adaptation to oxygen stress in Nile tilapia (Oreochromis niloticus) Chapter 3Quantitative trait loci controlling swimming performance and their effect on growth in Nile tilapia (Oreochromis niloticus)Chapter 4 Genomic analysis of a Nile tilapia strain selected...

show abstract

Genome-wide association analysis of adaptation to oxygen stress in Nile tilapia (Oreochromis niloticus)

Megens

Mengistu

et al. 2021

BMC Genomics

View full text Add to dashboard Cite

Background Tilapia is one of the most abundant species in aquaculture. Hypoxia is known to depress growth rate, but the genetic mechanism by which this occurs is unknown. In this study, two groups consisting of 3140 fish that were raised in either aerated (normoxia) or non-aerated pond (nocturnal hypoxia). During grow out, fish were sampled five times to determine individual body weight (BW) gains. We applied a genome-wide association study to identify SNPs and genes associated with the hypoxic and normoxic environments in the 16th generation of a Genetically Improved Farmed Tilapia population. Results In the hypoxic environment, 36 SNPs associated with at least one of the five body weight measurements (BW1 till BW5), of which six, located between 19.48 Mb and 21.04 Mb on Linkage group (LG) 8, were significant for body weight in the early growth stage (BW1 to BW2). Further significant associations were found for BW in the later growth stage (BW3 to BW5), located on LG1 and LG8. Analysis of genes within the candidate genomic region suggested that MAPK and VEGF signalling were significantly involved in the later growth stage under the hypoxic environment. Well-known hypoxia-regulated genes such as igf1rb, rora, efna3 and aurk were also associated with growth in the later stage in the hypoxic environment. Conversely, 13 linkage groups containing 29 unique significant and suggestive SNPs were found across the whole growth period under the normoxic environment. A meta-analysis showed that 33 SNPs were significantly associated with BW across the two environments, indicating a shared effect independent of hypoxic or normoxic environment. Functional pathways were involved in nervous system development and organ growth in the early stage, and oocyte maturation in the later stage. Conclusions There are clear genotype-growth associations in both normoxic and hypoxic environments, although genome architecture involved changed over the growing period, indicating a transition in metabolism along the way. The involvement of pathways important in hypoxia especially at the later growth stage indicates a genotype-by-environment interaction, in which MAPK and VEGF signalling are important components.

show abstract

Abstract 2431: EFNA3, a key functional mediator of hypoxic microenvironment in hepatocellular carcinoma

Cited by 3 publications

References 0 publications

Genome-wide Association Analysis of Adaptation to Oxygen Stress in Nile Tilapia (Oreochromis Niloticus)

Genome-wide Association Analysis of Adaptation to Oxygen Stress in Nile Tilapia (Oreochromis Niloticus)

Genomic architecture of selection for adaptation to challenging environments in aquaculture

Genome-wide association analysis of adaptation to oxygen stress in Nile tilapia (Oreochromis niloticus)

Contact Info

Product

Resources

About