Methionine-Homocysteine Pathway in African-American Prostate Cancer

Gohlke, Jie; Lloyd, Stacy M.; Basu, Sumanta; Putluri, Vasanta; Vareed, Shaiju K.; Rasaily, Uttam; Piyarathna, Danthasinghe Waduge Badrajee; Fuentes, Hunter; Rajendiran, Thekkelnaycke M.; Dorsey, Tiffany H.; Ambati, Chandrashekar R.; Sonavane, Rajni; Karanam, Balasubramanyam; Bhowmik, Salil Kumar; Kittles, Rick A.; Ambs, Stefan; Mims, Martha P.; Ittmann, Michael; Jones, Jeffrey A.; Palapattu, Ganesh S.; Putluri, Nagireddy; Michailidis, George; Sreekumar, Arun

doi:10.1093/jncics/pkz019

Cited by 24 publications

(27 citation statements)

References 8 publications

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“…Polyamines were extracted using the liquid‐liquid extraction method previously described. [ 86 , 87 , 88 ] The extracted samples were resuspended into methanol‐water (50:50 v/v) and subjected to chromatographic separation in hydrophilic interaction chromatography separation mode with XBridge Amide column (3.5 µm, 4.6 × 100 mm, ESI‐positive ionization, Waters, Milford, MA). Formic acid (0.1%) in water and acetonitrile were used as mobile phase A and B, respectively, as previously described.…”

Section: Methodsmentioning

confidence: 99%

CHAF1A Blocks Neuronal Differentiation and Promotes Neuroblastoma Oncogenesis via Metabolic Reprogramming

Tao

Moreno‐Smith

Ibarra‐García‐Padilla

et al. 2021

Advanced Science

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Neuroblastoma (NB) arises from oncogenic disruption of neural crest (NC) differentiation. Treatment with retinoic acid (RA) to induce differentiation has improved survival in some NB patients, but not all patients respond, and most NBs eventually develop resistance to RA. Loss of the chromatin modifier chromatin assembly factor 1 subunit p150 (CHAF1A) promotes NB cell differentiation; however, the mechanism by which CHAF1A drives NB oncogenesis has remained unexplored. This study shows that CHAF1A gain-of-function supports cell malignancy, blocks neuronal differentiation in three models (zebrafish NC, human NC, and human NB), and promotes NB oncogenesis. Mechanistically, CHAF1A upregulates polyamine metabolism, which blocks neuronal differentiation and promotes cell cycle progression. Targeting polyamine synthesis promotes NB differentiation and enhances the anti-tumor activity of RA. The authors' results provide insight into the mechanisms that drive NB oncogenesis and suggest a rapidly translatable therapeutic approach (DFMO plus RA) to enhance the clinical efficacy of differentiation therapy in NB patients.

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Section: Methodsmentioning

confidence: 99%

CHAF1A Blocks Neuronal Differentiation and Promotes Neuroblastoma Oncogenesis via Metabolic Reprogramming

Tao

Moreno‐Smith

Ibarra‐García‐Padilla

et al. 2021

Advanced Science

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“…However, the causal relationship between homocysteine and cancers remains controversial. For instance, certain observational studies suggest that homocysteine is a risk factor for some cancers, e.g., BRCA and prostate cancer (PrCa) (19,20). Other studies, however, suggest otherwise (21)(22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

“…Epidemiological/observational studies have limitations because of (potentially) biased results, limited cases, confounding factors, and reverse causation. It is interesting to note that published observational studies on the association of homocysteine, as a potential cancer biomarker, with risks of BRCA and PrCa have drawn inconsistent conclusions (19)(20)(21)(22)(23)(24). One limitation of these studies is that it is difficult to interpret the results with confounding and reverse causation.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Homocysteine on the Risk of Hormone-Related Cancers: A Mendelian Randomization Study

Yang

Sun

et al. 2021

Front. Nutr.

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Background: Aberrant homocysteine level is associated with metabolic disorders and DNA damage, which may be involved in the carcinogenesis of hormone-related cancers, but clinical results of observational studies are controversial. In this study, we investigated the causal relationships between plasma homocysteine and breast cancer (BRCA), prostate cancer (PrCa), and renal cell carcinoma (RCC) using Mendelian randomization (MR) analyses.Design and Methods: To investigate the putative causal associations between homocysteine and the aforementioned three types of cancers, a two-sample MR study was employed for the study. The primary strategy for summary data analyses was the inverse-variance-weighted (IVW) approach. In our study, the single-nucleotide polymorphisms (SNPs) excluded confounding factors through Linkage Disequilibrium (LD). Phenoscanner tests were the instrumental variants (IVs), homocysteine was the exposure, and BRCA, PrCa, and RCC were the outcomes. Single-nucleotide polymorphisms associated with homocysteine were extracted from a large genome-wide association study (GWAS) meta-analysis of European participants (n = 44,147). Summary Statistics of BRCA were obtained from the latest and largest GWAS meta-analysis comprising of 82 studies from Breast Cancer Association Consortium (BCAC) studies, including women of European ancestry (133,384 cases and 113,789 controls); we obtained summary-level data from the GWAS meta-analysis of PrCa comprising 79,148 cases and 61,106 controls of European ancestry, and the dataset of RCC was a sex-specific GWAS meta-analysis comprising of two kidney cancer genome-wide scans for men (3,227 cases and 4,916 controls) and women (1,992 cases and 3,095 controls) of European ancestry. The MR-Egger and weight median analyses were applied for the pleiotropy test.Results: The results showed null associations between plasma homocysteine levels and overall BRCA (effect = 0.97, 95% CI: 0.90–1.06, P = 0.543), overall PrCa (effect = 1.01, 95% CI: 0.93–1.11, P = 0.774), RCC in men (effect = 0.99, 95% CI: 0.73–1.34, P = 0.929), and RCC in women (effect = 0.89, 95% CI: 0.61–1.31, P = 0.563).Conclusions: We found no putative causal associations between homocysteine and risk of BRCA, PrCa, and RCC.

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“…All extraction protocols were described previously 4,5 . To ensure quality data, quality controls (liver tissue extract) were used to monitor the extraction efficiency, instrument variation, and reproducibility as described earlier 6 .…”

Section: Metabolomics Gas Chromatography-mass Spectrometry (Gc/ms) Array and Analysismentioning

confidence: 99%

Pancreatic Differentiation of Stem Cells Reveals Pathogenesis of a Syndrome of Ketosis-Prone Diabetes

et al. 2021

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Human dermal fibroblasts reprogramming to iPSCsFibroblasts were reprogrammed into iPSCs using a non-integration method based on modified mRNA 1 using a StemRNA reprogramming kit (StemGent; Cambridge, MA). Skin fibroblasts were plated at three different densities on irradiated feeder human dermal fibroblasts and transfected with modified mRNA encoding human OCT4, KLF4, SOX2, LIN28, c-MYC, and control GFP. The transfection was repeated daily over 10-14-day periods as iPSC colonies appeared. Newly derived iPSCs were passaged at least three times before banking. qPCR: RNA was extracted using the RNeasy Mini Kit (Qiagen; Hilden, Germany). cDNA was synthesized using KAPA cDNA Mix, and qPCR was performed using KAPA SYBR FAST (Kapa Biosystems; Indianapolis, Indiana) on a Connect CFX light cycler (Bio-Rad; Hercules, CA) with ≤40 PCR cycles. Using qPrimerDepot, primers were designed so the PCR products spanned exon junctions. Primer specificity was checked using CFX Manager Software v3.1 (Applied Biosystems; Foster City, CA) and PCR product agarose gel electrophoresis. Threshold data were analyzed with the CFX Manager Software v3.1 using the Comparative Ct relative quantitation method with TATA-Box binding protein as an internal control. Human induced pluripotent stem cells (iPSCs) maintenanceThe iPSCs were maintained on Matrigel (BD Biosciences; San Jose, CA) in Essential 8 media (E8, StemCell Technologies; Vancouver, Canada). Cells were passaged every 3-5 days at 80% confluency with TrypLE Express (Invitrogen, Carlsbad, CA). After passage, cells were kept in 10 µM Y-27632 (StemGent) for 24 h.

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Methionine-Homocysteine Pathway in African-American Prostate Cancer

Cited by 24 publications

References 8 publications

CHAF1A Blocks Neuronal Differentiation and Promotes Neuroblastoma Oncogenesis via Metabolic Reprogramming

CHAF1A Blocks Neuronal Differentiation and Promotes Neuroblastoma Oncogenesis via Metabolic Reprogramming

The Impact of Homocysteine on the Risk of Hormone-Related Cancers: A Mendelian Randomization Study

Pancreatic Differentiation of Stem Cells Reveals Pathogenesis of a Syndrome of Ketosis-Prone Diabetes

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