Neuroblastoma (NB) is the most common pediatric malignancy and is considered to possess cancer stem cells (CSCs) properties which can drive tumor initiation and metastasis. β-carotene 15,15'-oxygenase (BCO1) is the main enzyme that catalyzes the first step in vitamin A biosynthesis from pro-vitamin A carotenoids. Retinoids (vitamin A) play a critical role in NB differentiation. However, the biological functions of BCO1 in NB remained to be elucidated. Here, we investigated the effects of BCO1 on NB CSCs with stably expressing BCO1 in NB cells. We show that BCO1 significantly suppressed self-renewal and markers of NB CSCs. Moreover, BCO1 inhibited the metastatic potential of NB cells and suppressed the enzymatic activity and expression of MMPs, as well as expression of HIF-1α and its downstream targets. In vivo, BCO1 reduced the metastatic incidence and volumes of metastatic tumors and downregulated the expression of CSCs markers, MMPs, and HIF-1α in tumor tissues of a mouse xenograft model. A possible mechanism underlying the anti-cancer activities of BCO1 is proposed based on miRNAs sequencing array data which suggests a role for BCO1 in regulating miRNAs associated with neuronal differentiation, cell-cell adhesion, and the Wnt signaling pathway. Thus, our results demonstrate new chemotherapeutic roles for BCO1 in malignant NB that mediate suppression of cancer stemness and metastasis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jnutbio.2019.03.010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Common and rare genetic variation intersects with ancestry to influence human skin and plasma carotenoid concentrations.
medRxiv
December 2024
Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD.
Carotenoids are dietary bioactive compounds with health effects that are biomarkers of fruit and vegetable intake. Here, we examine genetic associations with plasma and skin carotenoid concentrations in two rigorously phenotyped human cohorts (n=317). Analysis of genome-wide SNPs revealed heritability to vary by genetic ancestry (h=0.
View Article and Find Full Text PDFHepatic and intestinal insights into the molecular mechanisms of dietary Antarctic krill-induced body color differentiation in Plectropomus leopardus.
Genomics
January 2025
MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences/Key Laboratory of Tropical Aquatic Germplasm of Hainan Province, Sanya Oceanographic Institution, Ocean University of China, Qingdao/Sanya, China; Southern Marine Science and Engineer Guangdong Laboratory, Guangzhou 511458, China. Electronic address:
Antarctic krill (Euphausia superba), which is rich in astaxanthin, has been widely utilized as a dietary supplement in fish aquaculture. Our study was to feed juvenile leopard coral grouper (Plectropomus leopardus) a diet containing 50 % Antarctic krill, revealing significant body color differentiation between a reddened group (BKR) and a non-reddened group (BKB), followed by comparative analysis with the control group (BCon) without krill supplementation. Histological analysis and carotenoid content in the liver and intestine were differentially regulated in color-differentiated individuals.
View Article and Find Full Text PDFGenetic variants in the PKD1L2/BCO1 region are associated with β-carotene, lutein, and zeaxanthin: A genome-wide association study of plasma carotenoids.
Nutr Res
December 2024
Department of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada. Electronic address:
Article Synopsis
- Carotenoid consumption is linked to a lower risk of chronic diseases, and genetic differences may explain varying levels of carotenoids in people's blood.
- A study on young Caucasian adults aimed to find genetic variants related to different plasma carotenoids and included diverse ethnic replication groups to validate findings.
- While previously identified genetic associations were replicated, no new significant associations were found, indicating a need for further research to understand individual nutritional needs for carotenoids.
Association between two common SNPs, rs6564851 and rs6420424, and lutein and zeaxanthin levels in a cohort of US postmenopausal women with a family history of breast cancer.
Front Nutr
October 2024
Department of Epidemiology, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
A better understanding of the factors contributing to systemic concentrations of carotenoids is necessary given the weak correlations between circulating levels and dietary intake of carotenoids. Although genetic variation may play a key role in the interindividual variability in carotenoid concentrations, few genome-wide association studies (GWAS) have focused on carotenoids. We used a random sample ( = 519) of postmenopausal participants in the Sister Study with data on genotypes and plasma carotenoid levels to conduct GWAS for each of five carotenoids (mcg/mL): alpha-carotene, beta- carotene, cryptoxanthin, lycopene, and lutein/zeaxanthin.
View Article and Find Full Text PDFLncRNA (BCO1-AS) regulate inflammatory responses in bacterial infection through caspase-1 in turbot (Scophthalmus maximus).
Int J Biol Macromol
November 2024
School of Marine Science and Engineering, Qingdao Agricultural University, Qingdao 266109, China. Electronic address:
LncRNA plays key role in several biological processes, including transcriptional regulation, post transcriptional control and epigenetic regulation. However, research on the functional roles of lncRNAs in teleost species remains limited. Here, we discovered a lncRNA (BCO1-AS) with a critical role in antibacterial responses.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!