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Skalny AV, Kushlinskii NE, Korobeinikova TV, Alferov AA, Kuzmin YB, Kochkina SO, Gordeev SS, Mammadli ZZ, Stilidi IS, Tinkov AA. Zinc, copper, copper-to-zinc ratio, and other biometals in blood serum and tumor tissue of patients with colorectal cancer. Biometals 2025; 38:529-544. [PMID: 39820949 DOI: 10.1007/s10534-024-00660-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 12/24/2024] [Indexed: 01/19/2025]
Abstract
The objective of the present study was to assess serum and cancerous tissue biometal levels in colorectal cancer (CRC) patients, and its relation to disease severity. A total of 90 CRC patients and 97 controls were involved in the present study. The level of biometals in blood serum and colon tissues (only in CRC cases) was evaluated by inductively-coupled plasma mass-spectrometry. CRC patients are characterized by lower serum Ca, Fe, Se, and Zn, as well as higher serum Co, Cu, Mg, V, and Cu/Zn ratio compared to healthy controls. The lowest serum Zn levels and the highest Cu concentration and Cu/Zn ratio were observed in patients with the largest tumor size. Regression analysis demonstrated that tumor size is a significant negative predictor of serum Se levels, being positively associated with serum Cu/Zn values. The degree of metastasis to regional lymph nodes was inversely associated with circulating Ca, Co, Mg, Zn, and Mn levels. Serum Mg and Mn levels were positively associated with the stage of the disease and tumor location, respectively. Cancerous tissue Ca and Mo levels were lower, while Mg content was higher compared to healthy adjacent tissues. In cancerous tissues a constant but non-significant trend to elevation of tissue Zn content with increasing tumor size was observed. In addition, serum Cu, Zn, and Cu/Zn values positively correlated with the respective tumor values. These findings demonstrate that altered biometal metabolism is associated with CRC, while systemic Cu/Zn ratio may be indicative of Cu and Zn imbalance in cancerous tissue.
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Affiliation(s)
- Anatoly V Skalny
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, 119991, Russia
- Peoples Friendship University of Russia (RUDN University), Moscow, 117198, Russia
| | | | - Tatiana V Korobeinikova
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, 119991, Russia
- Peoples Friendship University of Russia (RUDN University), Moscow, 117198, Russia
| | - Aleksandr A Alferov
- N.N. Blokhin National Medical Research Center of Oncology, Moscow, 115478, Russia
- Russian University of Medicine, Moscow, 127473, Russia
| | | | - Sofya O Kochkina
- N.N. Blokhin National Medical Research Center of Oncology, Moscow, 115478, Russia
| | - Sergey S Gordeev
- N.N. Blokhin National Medical Research Center of Oncology, Moscow, 115478, Russia
| | - Zaman Z Mammadli
- N.N. Blokhin National Medical Research Center of Oncology, Moscow, 115478, Russia
| | - Ivan S Stilidi
- N.N. Blokhin National Medical Research Center of Oncology, Moscow, 115478, Russia
| | - Alexey A Tinkov
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, 119991, Russia.
- Peoples Friendship University of Russia (RUDN University), Moscow, 117198, Russia.
- P.G. Demidov Yaroslavl State University, Yaroslavl, 150003, Russia.
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Cai X, Su Y, Ning J, Fan X, Shen M. Research on the Effect and Mechanism of Selenium on Colorectal Cancer Through TRIM32. Biol Trace Elem Res 2025; 203:670-683. [PMID: 38691306 DOI: 10.1007/s12011-024-04206-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Accepted: 04/24/2024] [Indexed: 05/03/2024]
Abstract
The intake of selenium (Se) in the human body is negatively correlated with the risk of colorectal cancer (CRC), but its mechanism in the occurrence and development of CRC is not clear. This study aimed to evaluate the therapeutic effect of Se on CRC, and explore the anti-tumor effect of Se supplementation on CRC and its molecular mechanism. In this study, we utilized colony formation assay, cell scratch test, Transwell migration, and flow cytometry to assess cell proliferation, migration, and apoptosis. Our findings demonstrate that Se effectively suppresses the growth and proliferation of CRC cell lines HCT116 and SW480 and promoting cellular apoptosis. In vivo experiments demonstrated a significant inhibitory effect of Se on tumor growth. CRC-related datasets were extracted from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases for differential expression analysis of TRIM32 and survival analysis. We found that TRIM32 was highly expressed in tumor tissues of CRC patients and correlated with a poor prognosis. Furthermore, through RNA sequencing analysis, we identified TRIM32 as a gene that was significantly decreased after Se treatment in HCT116 cells. This finding was subsequently validated by Western blot results. Moreover, TRIM32 knockdown combined with Se treatment significantly inhibited cell growth proliferation and migration and further induced apoptosis of colorectal cancer cells. In conclusion, our findings provided evidence that Se inhibited the growth of colorectal cancer cells by down-regulating TRIM32.
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Affiliation(s)
- Xiaohua Cai
- Department of Hygiene Inspection & Quarantine Science, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China
| | - Yintong Su
- Department of Hygiene Inspection & Quarantine Science, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China
| | - Jiayu Ning
- Department of Hygiene Inspection & Quarantine Science, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China
| | - Xingxing Fan
- Department of Hygiene Inspection & Quarantine Science, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China
| | - Mei Shen
- Department of Hygiene Inspection & Quarantine Science, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China.
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Hughes DJ, Schomburg L, Jenab M, Biessy C, Méplan C, Moskal A, Sun Q, Demircan K, Fedirko V, Weiderpass E, Mukhtar M, Olsen A, Tjønneland A, Overvad K, Schulze M, Nøst TH, Skeie G, Olsen KS, Ricceri F, Grioni S, Palli D, Masala G, Tumino R, Pasanisi F, Amiano P, Colorado Yohar SM, Agudo A, Sánchez MJ, Ardanaz E, Sund M, Andersson A, Perez-Cornago A, Travis R, Heath AK, Dossus L. Prediagnostic selenium status, selenoprotein gene variants and association with breast cancer risk in a European cohort study. Free Radic Biol Med 2023; 209:381-393. [PMID: 37923090 DOI: 10.1016/j.freeradbiomed.2023.10.401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 10/10/2023] [Accepted: 10/19/2023] [Indexed: 11/07/2023]
Abstract
Selenium (Se) may help prevent breast cancer (BC) development. Owing to limited observational evidence, we investigated whether prediagnostic Se status and/or variants in the selenoprotein genes are associated with BC risk in a large European cohort. Se status was assessed by plasma measures of Se and its major circulating proteins, selenoprotein P (SELENOP) and glutathione peroxidase 3 (GPX3), in matched BC case-control pairs (2208 for SELENOP; 1785 for GPX3 and Se) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Single nucleotide polymorphisms (SNPs, n = 452) in 55 selenoprotein and Se metabolic pathway genes and an additional 18 variants previously associated with Se concentrations were extracted from existing genotyping data within EPIC for 1564 case-control pairs. Multivariable-adjusted logistic regression models were used to calculate the odds ratios (ORs) and 95 % confidence intervals (CIs) of the association between Se status markers, SNP variants and BC risk. Overall, there was no statistically significant association of Se status with BC risk. However, higher GPX3 activity was associated with lower risk of premenopausal BC (4th versus 1st quartile, OR = 0.54, 95 % CI: 0.30-0.98, Ptrend = 0.013). While none of the genetic variant associations (P ≤ 0.05) retained significance after multiple testing correction, rs1004243 in the SELENOM selenoprotein gene and two SNPs in the related antioxidant TXN2 gene (rs4821494 and rs5750261) were associated with respective lower and higher risks of BC at a significance threshold of P ≤ 0.01. Fourteen SNPs in twelve Se pathway genes (P ≤ 0.01) in interaction with Se status were also associated with BC risk. Higher Se status does not appear to be associated with BC risk, although activity of the selenoenzyme GPX3 may be inversely associated with premenopausal BC risk, and SNPs in the Se pathway alone or in combination with suboptimal Se status may influence BC risk.
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Affiliation(s)
- David J Hughes
- Cancer Biology and Therapeutics Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland.
| | - Lutz Schomburg
- Institute for Experimental Endocrinology, Charité - Medical University, Berlin, Germany
| | - Mazda Jenab
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Carine Biessy
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Catherine Méplan
- School of Biomedical, Nutritional and Sport Sciences, Newcastle University, Newcastle Upon Tyne, UK
| | - Aurelie Moskal
- International Agency for Research on Cancer (IARC-WHO), Lyon, France; Research on Healthcare Performance (RESHAPE), INSERM U1290, Université Claude Bernard Lyon 1, Lyon, France
| | - Qian Sun
- Institute for Experimental Endocrinology, Charité - Medical University, Berlin, Germany
| | - Kamil Demircan
- Institute for Experimental Endocrinology, Charité - Medical University, Berlin, Germany
| | - Veronika Fedirko
- Department of Epidemiology, MD Anderson Cancer Centre, Houston, TX, USA
| | | | - Maryam Mukhtar
- Cancer Biology and Therapeutics Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland
| | - Anja Olsen
- Diet, Genes, and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark; Institute of Public Health, Aarhus University, Aarhus, Denmark
| | - Anne Tjønneland
- Diet, Genes, and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark; Institute of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Kim Overvad
- Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark; Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Matthias Schulze
- Department of Molecular Epidemiology, German Institute of Human Nutrition, 14558, Nuthetal, Germany
| | - Therese Haugdahl Nøst
- Department of Community Medicine, UiT the Arctic University of Norway, N-9037, Tromsø, Norway
| | - Guri Skeie
- Department of Community Medicine, UiT the Arctic University of Norway, N-9037, Tromsø, Norway
| | - Karina Standahl Olsen
- Department of Community Medicine, UiT the Arctic University of Norway, N-9037, Tromsø, Norway
| | - Fulvio Ricceri
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco, TO, Italy
| | - Sara Grioni
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori di Milano, 20133, Milano, Italy
| | - Domenico Palli
- Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy
| | - Giovanna Masala
- Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy
| | - Rosario Tumino
- Hyblean Association for Epidemiological Research, AIRE ONLUS Ragusa, Italy
| | - Fabrizio Pasanisi
- Departiment Di Medicina Clinica E Chirurgia Federico Ii University, Naples, Italy
| | - Pilar Amiano
- Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa, San Sebastian, Spain; Biodonostia Health Research Institute, Epidemiology of Chronic and Communicable Diseases Group, San Sebastián, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain
| | - Sandra M Colorado Yohar
- Department of Epidemiology, Murcia Regional Health Council, IMIB, Murcia, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia
| | - Antonio Agudo
- Unit of Nutrition and Cancer, Catalan Institute of Oncology - ICO, L'Hospitalet de Llobregat, Spain; Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute - IDIBELL, L'Hospitalet de Llobregat, Spain
| | - Maria-Jose Sánchez
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Escuela Andaluza de Salud Pública (EASP), 18011, Granada, Spain; Instituto de Investigación Biosanitaria Ibs.GRANADA, 18012, Granada, Spain; Department of Preventive Medicine and Public Health, University of Granada, 18071, Granada, Spain
| | - Eva Ardanaz
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Navarra Public Health Institute, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
| | - Malin Sund
- Department of Surgery and Perioperative Sciences, Umeå University, Umeå, Sweden; Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Anne Andersson
- Department of Radiation Sciences/Oncology, Umeå University, Umeå, Sweden
| | - Aurora Perez-Cornago
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK
| | - Ruth Travis
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK
| | - Alicia K Heath
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Laure Dossus
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
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Fu X, Deng Y, Xu H, Shu Y, Chen HN. Selenium metabolism heterogeneity in pan-cancer: insights from bulk and single-cell RNA sequencing. J Cancer Res Clin Oncol 2023; 149:15535-15551. [PMID: 37648807 DOI: 10.1007/s00432-023-05333-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 08/21/2023] [Indexed: 09/01/2023]
Abstract
BACKGROUND Selenium, a natural microelement with both nutritional and toxicological properties, is intertwined with tumorigenesis and progression. However, it is not fully understood how selenium metabolism affects immune response and cancer biology. METHODS We estimated selenium metabolism by Gene Set Enrichment Analysis (GSEA) to delineate the selenium metabolism landscape using The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE) and a integrated pan-cancer single-cell dataset. We systematically explored the prognostic implications of selenium metabolism and selenium-related regulatory patterns. The therapeutic value of selenium metabolism was explored through machine learning and examined in several immunotherapy cohorts. The heterogeneity and underlying mechanism of selenium metabolism were investigated by cell‒cell communication analysis at the single-cell level. RESULTS A GSEA analysis based on 86 genes was used to evaluate the selenium metabolism landscape. The selenium metabolism score exhibited prognostic value in predicting the lower risk of mortality, possibly due to its correlation with multiple cancer hallmarks, including a positive correlation with complement (R = 0.761, P < 0.001), inflammatory response (R = 0.663, P < 0.001), apoptosis (R = 0.626, P < 0.001), hypoxia (R = 0.587, P < 0.001), reactive oxygen species (ROS) (R = 0.558, P < 0.001), and interferon gamma response (R = 0.539, P < 0.001). We also observed heterogeneity in the relationship between selenium metabolism and immunity across different cancers. Based on selenium-related genes, we constructed a machine learning model with area under the ROC curve (AUC) of 0.82 in predicting immune checkpoint inhibitor (ICI)-based immunotherapy response. Single-cell selenium metabolism quantification revealed that adjacent and tumor tissues had higher selenium metabolism compared with normal tissues, especially in epithelial cells, fibroblasts and macrophages. The communication between high-selenium epithelium and high-selenium fibroblast was significantly higher than other cells, especially in cytokines, chemokines, collagen, Wnt, VEGF, IGF and FGF pathways. CONCLUSION Our study provides a comprehensive landscape of selenium metabolism levels and diverse regulatory patterns in different cancers, deepening the understanding of selenium's roles in tumorigenesis and immunity.
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Affiliation(s)
- Xiaorui Fu
- Department of General Surgery, Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yiqi Deng
- Department of General Surgery, Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, China
- State Key Laboratory of Biotherapy, Department of Biotherapy and Cancer Center, West China Hospital, Chengdu, China
| | - Heng Xu
- State Key Laboratory of Biotherapy, Department of Biotherapy and Cancer Center, West China Hospital, Chengdu, China
| | - Yang Shu
- Department of General Surgery, Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
| | - Hai-Ning Chen
- Department of General Surgery, Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
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Barbosa P, Abo El-Magd NF, Hesketh J, Bermano G. The Role of rs713041 Glutathione Peroxidase 4 ( GPX4) Single Nucleotide Polymorphism on Disease Susceptibility in Humans: A Systematic Review and Meta-Analysis. Int J Mol Sci 2022; 23:15762. [PMID: 36555402 PMCID: PMC9778852 DOI: 10.3390/ijms232415762] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 12/06/2022] [Accepted: 12/08/2022] [Indexed: 12/15/2022] Open
Abstract
Aim: The single-nucleotide polymorphism (SNP) rs713041, located in the regulatory region, is required to incorporate selenium into the selenoprotein glutathione peroxidase 4 (GPX4) and has been found to have functional consequences. This systematic review aimed to conduct a meta-analysis to determine whether there is an association between GPX4 (rs713041) SNP and the risk of diseases in humans and its correlation with selenium status. Material and methods: A systematic search for English-language manuscripts published between January 1990 and November 2022 was carried out using six databases: CINAHL, Cochrane, Medline, PubMed, Scopus and Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to assess a relationship between GPX4 (rs713041) SNP and the risk of different diseases based on three genetic models. Review Manager 5.4 and Comprehensive Meta-Analysis 4 software were used to perform the meta-analysis and carry out Egger’s test for publication bias. Results: Data from 21 articles were included in the systematic review. Diseases were clustered according to the physiological system affected to understand better the role of GPX4 (rs713041) SNP in developing different diseases. Carriers of the GPX4 (rs173041) T allele were associated with an increased risk of developing colorectal cancer in additive and dominant models (p = 0.02 and p = 0.004, respectively). In addition, carriers of the T allele were associated with an increased risk of developing stroke and hypertension in the additive, dominant and recessive models (p = 0.002, p = 0.004 and p = 0.01, respectively). On the other hand, the GPX4 (rs713041) T allele was associated with a decreased risk of developing pre-eclampsia in the additive, dominant and recessive models (p < 0.0001, p = 0.002 and p = 0.0005, respectively). Moreover, selenium levels presented lower mean values in cancer patients relative to control groups (SMD = −0.39 µg/L; 95% CI: −0.64, −0.14; p = 0.002, I2 = 85%). Conclusion: GPX4 (rs713041) T allele may influence colorectal cancer risk, stroke, hypertension and pre-eclampsia. In addition, low selenium levels may play a role in the increased risk of cancer.
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Affiliation(s)
- Priscila Barbosa
- Centre for Obesity Research and Education (CORE), School of Pharmacy and Life Sciences, Robert Gordon University, Sir Ian Wood Building, Garthdee Road, Aberdeen AB10 7GJ, UK
| | - Nada F. Abo El-Magd
- Biochemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - John Hesketh
- Centre for Obesity Research and Education (CORE), School of Pharmacy and Life Sciences, Robert Gordon University, Sir Ian Wood Building, Garthdee Road, Aberdeen AB10 7GJ, UK
| | - Giovanna Bermano
- Centre for Obesity Research and Education (CORE), School of Pharmacy and Life Sciences, Robert Gordon University, Sir Ian Wood Building, Garthdee Road, Aberdeen AB10 7GJ, UK
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Lee MY, Ojeda-Britez S, Ehrbar D, Samwer A, Begley TJ, Melendez JA. Selenoproteins and the senescence-associated epitranscriptome. Exp Biol Med (Maywood) 2022; 247:2090-2102. [PMID: 36036467 PMCID: PMC9837304 DOI: 10.1177/15353702221116592] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
Selenium is a naturally found trace element, which provides multiple benefits including antioxidant, anticancer, and antiaging, as well as boosting immunity. One unique feature of selenium is its incorporation as selenocysteine, a rare 21st amino acid, into selenoproteins. Twenty-five human selenoproteins have been discovered, and a majority of these serve as crucial antioxidant enzymes for redox homeostasis. Unlike other amino acids, incorporation of selenocysteine requires a distinctive UGA stop codon recoding mechanism. Although many studies correlating selenium, selenoproteins, aging, and senescence have been performed, it has not yet been explored if the upstream events regulating selenoprotein synthesis play a role in senescence-associated pathologies. The epitranscriptomic writer alkylation repair homolog 8 (ALKBH8) is critical for selenoprotein production, and its deficiency can significantly decrease levels of selenoproteins that are essential for reactive oxygen species (ROS) detoxification, and increase oxidative stress, one of the major drivers of cellular senescence. Here, we review the potential role of epitranscriptomic marks that govern selenocysteine utilization in regulating the senescence program.
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Affiliation(s)
- May Y Lee
- College of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, NY 12203, USA
- The RNA Institute, University at Albany, Albany, NY 12222, USA
| | - Stephen Ojeda-Britez
- College of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, NY 12203, USA
| | - Dylan Ehrbar
- The RNA Institute, University at Albany, Albany, NY 12222, USA
- Department of Biological Sciences, University at Albany, Albany, NY 12222, USA
- RNA Epitranscriptomics and Proteomics Resource, University at Albany, Albany, NY 12222, USA
| | | | - Thomas J Begley
- The RNA Institute, University at Albany, Albany, NY 12222, USA
- Department of Biological Sciences, University at Albany, Albany, NY 12222, USA
- RNA Epitranscriptomics and Proteomics Resource, University at Albany, Albany, NY 12222, USA
| | - J Andres Melendez
- College of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, NY 12203, USA
- The RNA Institute, University at Albany, Albany, NY 12222, USA
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Dávila-Vega JP, Gastelum-Hernández AC, Serrano-Sandoval SN, Serna-Saldívar SO, Guitiérrez-Uribe JA, Milán-Carrillo J, Martínez-Cuesta MC, Guardado-Félix D. Metabolism and Anticancer Mechanisms of Selocompounds: Comprehensive Review. Biol Trace Elem Res 2022:10.1007/s12011-022-03467-1. [PMID: 36342630 DOI: 10.1007/s12011-022-03467-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 10/26/2022] [Indexed: 11/09/2022]
Abstract
Selenium (Se) is an essential micronutrient with several functions in cellular and molecular anticancer processes. There is evidence that Se depending on its chemical form and the dosage use could act as a modulator in some anticancer mechanisms. However, the metabolism of organic and inorganic forms of dietary selenium converges on the main pathways. Different selenocompounds have been reported to have crucial roles as chemopreventive agents, such as antioxidant activity, activation of apoptotic pathways, selective cytotoxicity, antiangiogenic effect, and cell cycle modulation. Nowadays, great interest has arisen to find therapies that could enhance the antitumor effects of different Se sources. Herein, different studies are reported related to the effects of combinatorial therapies, where Se is used in combination with proteins, polysaccharides, chemotherapeutic agents or as nanoparticles. Another important factor is the presence of single nucleotide polymorphisms in genes related to Se metabolism or selenoprotein synthesis which could prevent cancer. These studies and mechanisms show promising results in cancer therapies. This review aims to compile studies that have demonstrated the anticancer effects of Se at molecular levels and its potential to be used as chemopreventive and in cancer treatment.
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Affiliation(s)
- Juan Pablo Dávila-Vega
- Escuela de Ingeniería Y Ciencias, Centro de Biotecnología FEMSA, Tecnológico de Monterrey, Av. Eugenio Garza Sada 2501 Sur, C.P. 64849, Monterrey, NL, México
- Tecnologico de Monterrey, The Institute for Obesity Research, Av. Eugenio Garza Sada 2501 Sur, C.P. 64849, Monterrey, NL, Mexico
| | - Ana Carolina Gastelum-Hernández
- Facultad de Ciencias Químico Biológicas, Programa Regional de Posgrado en Biotecnología, Universidad Autónoma de Sinaloa, FCQB-UAS, AP 1354, CP 80000, Culiacán, Sinaloa, Mexico
| | - Sayra N Serrano-Sandoval
- Escuela de Ingeniería Y Ciencias, Centro de Biotecnología FEMSA, Tecnológico de Monterrey, Av. Eugenio Garza Sada 2501 Sur, C.P. 64849, Monterrey, NL, México
- Tecnologico de Monterrey, The Institute for Obesity Research, Av. Eugenio Garza Sada 2501 Sur, C.P. 64849, Monterrey, NL, Mexico
| | - Sergio O Serna-Saldívar
- Escuela de Ingeniería Y Ciencias, Centro de Biotecnología FEMSA, Tecnológico de Monterrey, Av. Eugenio Garza Sada 2501 Sur, C.P. 64849, Monterrey, NL, México
| | - Janet A Guitiérrez-Uribe
- Tecnologico de Monterrey, The Institute for Obesity Research, Av. Eugenio Garza Sada 2501 Sur, C.P. 64849, Monterrey, NL, Mexico
- Escuela de Ingeniería Y Ciencias, Tecnologico de Monterrey, Reserva Territorial Atlixcáyotl, Campus Puebla, Vía Atlixcáyotl 5718, C.P. 72453, Puebla, Pue, México
| | - Jorge Milán-Carrillo
- Tecnologico de Monterrey, The Institute for Obesity Research, Av. Eugenio Garza Sada 2501 Sur, C.P. 64849, Monterrey, NL, Mexico
| | - M Carmen Martínez-Cuesta
- Department of Food Biotechnology and Microbiology, Instituto de Investigación en Ciencias de La Alimentación, CIAL (CSIC-UAM), Nicolás Cabrera 9, 28049, Madrid, Spain
| | - Daniela Guardado-Félix
- Escuela de Ingeniería Y Ciencias, Centro de Biotecnología FEMSA, Tecnológico de Monterrey, Av. Eugenio Garza Sada 2501 Sur, C.P. 64849, Monterrey, NL, México.
- Tecnologico de Monterrey, The Institute for Obesity Research, Av. Eugenio Garza Sada 2501 Sur, C.P. 64849, Monterrey, NL, Mexico.
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8
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Ehudin MA, Golla U, Trivedi D, Potlakayala SD, Rudrabhatla SV, Desai D, Dovat S, Claxton D, Sharma A. Therapeutic Benefits of Selenium in Hematological Malignancies. Int J Mol Sci 2022; 23:ijms23147972. [PMID: 35887320 PMCID: PMC9323677 DOI: 10.3390/ijms23147972] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 07/09/2022] [Accepted: 07/12/2022] [Indexed: 12/14/2022] Open
Abstract
Supplementing chemotherapy and radiotherapy with selenium has been shown to have benefits against various cancers. This approach has also been shown to alleviate the side effects associated with standard cancer therapies and improve the quality of life in patients. In addition, selenium levels in patients have been correlated with various cancers and have served as a diagnostic marker to track the efficiency of treatments or to determine whether these selenium levels cause or are a result of the disease. This concise review presents a survey of the selenium-based literature, with a focus on hematological malignancies, to demonstrate the significant impact of selenium in different cancers. The anti-cancer mechanisms and signaling pathways regulated by selenium, which impart its efficacious properties, are discussed. An outlook into the relationship between selenium and cancer is highlighted to guide future cancer therapy development.
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Affiliation(s)
- Melanie A. Ehudin
- Division of Hematology and Oncology, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (M.A.E.); (S.D.)
| | - Upendarrao Golla
- Division of Hematology and Oncology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (U.G.); (D.C.)
- Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (D.T.); (D.D.)
| | - Devnah Trivedi
- Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (D.T.); (D.D.)
| | - Shobha D. Potlakayala
- Department of Biological Sciences, School of Science Engineering and Technology, Penn State Harrisburg, Middletown, PA 17057, USA; (S.D.P.); (S.V.R.)
| | - Sairam V. Rudrabhatla
- Department of Biological Sciences, School of Science Engineering and Technology, Penn State Harrisburg, Middletown, PA 17057, USA; (S.D.P.); (S.V.R.)
| | - Dhimant Desai
- Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (D.T.); (D.D.)
- Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
| | - Sinisa Dovat
- Division of Hematology and Oncology, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (M.A.E.); (S.D.)
| | - David Claxton
- Division of Hematology and Oncology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (U.G.); (D.C.)
- Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (D.T.); (D.D.)
| | - Arati Sharma
- Division of Hematology and Oncology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (U.G.); (D.C.)
- Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (D.T.); (D.D.)
- Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
- Correspondence:
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9
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Trejo MJ, Batai K, Chen Y, Brezina S, Chow HHS, Ellis N, Lance P, Hsu CH, Pogreba-Brown K, Bishop M, Gsur A, Jacobs ET. Genome-Wide Association Study of Metachronous Colorectal Adenoma Risk among Participants in the Selenium Trial. Nutr Cancer 2022; 75:143-153. [PMID: 35815403 PMCID: PMC10120393 DOI: 10.1080/01635581.2022.2096910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 06/02/2022] [Accepted: 06/28/2022] [Indexed: 12/15/2022]
Abstract
Genetic variants related to colorectal adenoma may help identify those who are at highest risk of colorectal cancer development or illuminate potential chemopreventive strategies. The purpose of this genome-wide association study was to identify genetic variants that are associated with risk of developing a metachronous colorectal adenoma among 1,215 study participants of European descent from the Selenium Trial. Associations of variants were assessed with logistic regression analyses and validated in an independent case-control study population of 1,491 participants from the Colorectal Cancer Study of Austria (CORSA). No statistically significant genome-wide associations between any variant and metachronous adenoma were identified after correction for multiple comparisons. However, an intron variant of FAT3 gene, rs61901554, showed a suggestive association (P = 1.10 × 10-6) and was associated with advanced adenomas in CORSA (P = 0.04). Two intronic variants, rs12728998 and rs6699944 in NLRP3 were also observed to have suggestive associations with metachronous lesions (P = 2.00 × 10-6) in the Selenium Trial and were associated with advanced adenoma in CORSA (P = 0.03). Our results provide new areas of investigation for the genetic basis of the development of metachronous colorectal adenoma and support a role for FAT3 involvement in the Wnt/β-catenin pathway leading to colorectal neoplasia.Trial Registration number: NCT00078897 (ClinicalTrials.gov).
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Affiliation(s)
- Mario Jesus Trejo
- Department of Epidemiology and Biostatistics, University of Arizona, Tucson, AZ, USA
| | - Ken Batai
- Department of Urology, University of Arizona, Tucson, AZ, USA
| | - Yuliang Chen
- Department of Epidemiology and Biostatistics, University of Arizona, Tucson, AZ, USA
| | - Stefanie Brezina
- Center for Cancer Research, Medical University of Vienna, Vienna, Austria
| | - H-H Sherry Chow
- University of Arizona Cancer Center, Tucson, AZ, USA
- Department of Molecular and Cellular Biology, College of Science, University of Arizona, Tucson, AZ, USA
| | - Nathan Ellis
- Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA
| | - Peter Lance
- University of Arizona Cancer Center, Tucson, AZ, USA
- Department of Molecular and Cellular Biology, College of Science, University of Arizona, Tucson, AZ, USA
| | - Chiu-Hsieh Hsu
- Department of Epidemiology and Biostatistics, University of Arizona, Tucson, AZ, USA
| | - Kristen Pogreba-Brown
- Department of Epidemiology and Biostatistics, University of Arizona, Tucson, AZ, USA
| | - Maria Bishop
- Department of Medicine, College of Medicine, University of Arizona, Tucson, AZ, USA
| | - Andrea Gsur
- Center for Cancer Research, Medical University of Vienna, Vienna, Austria
| | - Elizabeth T Jacobs
- Department of Epidemiology and Biostatistics, University of Arizona, Tucson, AZ, USA
- University of Arizona Cancer Center, Tucson, AZ, USA
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10
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Mukhtar M, Ashfield N, Vodickova L, Vymetalkova V, Levy M, Liska V, Bruha J, Bendova P, O’Sullivan J, Doherty G, Sheahan K, Nolan B, Vodicka P, Hughes DJ. The Associations of Selenoprotein Genetic Variants with the Risks of Colorectal Adenoma and Colorectal Cancer: Case–Control Studies in Irish and Czech Populations. Nutrients 2022; 14:nu14132718. [PMID: 35807897 PMCID: PMC9268344 DOI: 10.3390/nu14132718] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 06/27/2022] [Indexed: 02/05/2023] Open
Abstract
Background: Selenium manifests its biological effects through its incorporation into selenoproteins, which play several roles in countering oxidative and inflammatory responses implicated in colorectal carcinogenesis. Selenoprotein genetic variants may contribute to colorectal cancer (CRC) development, as we previously observed for SNP variants in a large European prospective study and a Czech case–control cohort. Methods: We tested if significantly associated selenoprotein gene SNPs from these studies were also associated with CRC risk in case–control studies from Ireland (colorectal neoplasia, i.e., cancer and adenoma cases: 450, controls: 461) and the Czech Republic (CRC cases: 718, controls: 646). Genotyping of 23 SNPs (20 in the Irish and 13 in the Czechs) was performed by competitive specific allele-specific PCR (KASPar). Multivariable adjusted logistic regression was used to assess the associations with CRC development. Results: We found significant associations with an increased CRC risk for rs5859 (SELENOF) and rs2972994 (SELENOP) in the Irish cohort but only with rs4802034 (SELENOV) in the Czechs. Significant associations were observed for rs5859 (SELENOF), rs4659382 (SELENON), rs2972994 (SELENOP), rs34713741 (SELENOS), and the related Se metabolism gene variant rs2275129 (SEPHS1) with advanced colorectal neoplasia development. However, none of these findings retained significance after multiple testing corrections. Conclusions: Several SNPs previously associated with CRC risk were also associated with CRC or colorectal neoplasia development in either the Irish or Czech cohorts. Selenoprotein gene variation may modify CRC risk across diverse European populations, although the specific variants may differ.
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Affiliation(s)
- Maryam Mukhtar
- Cancer Biology and Therapeutics Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland; (M.M.); (N.A.)
| | - Niall Ashfield
- Cancer Biology and Therapeutics Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland; (M.M.); (N.A.)
| | - Ludmila Vodickova
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, 121 08 Prague, Czech Republic; (L.V.); (V.V.); (P.V.)
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, 323 00 Pilsen, Czech Republic; (V.L.); (J.B.)
- Institute of Experimental Medicine ASCR, 142 20 Prague, Czech Republic;
| | - Veronika Vymetalkova
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, 121 08 Prague, Czech Republic; (L.V.); (V.V.); (P.V.)
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, 323 00 Pilsen, Czech Republic; (V.L.); (J.B.)
- Institute of Experimental Medicine ASCR, 142 20 Prague, Czech Republic;
| | - Miroslav Levy
- Department of Surgery, First Faculty of Medicine, Charles University and Thomayer Hospital, 121 08 Prague, Czech Republic;
| | - Václav Liska
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, 323 00 Pilsen, Czech Republic; (V.L.); (J.B.)
| | - Jan Bruha
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, 323 00 Pilsen, Czech Republic; (V.L.); (J.B.)
- Institute of Experimental Medicine ASCR, 142 20 Prague, Czech Republic;
| | - Petra Bendova
- Institute of Experimental Medicine ASCR, 142 20 Prague, Czech Republic;
| | - Jacintha O’Sullivan
- Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin and St. James’s Hospital, D08 NHY1 Dublin, Ireland;
| | - Glen Doherty
- Centre for Colorectal Disease, St. Vincent’s University Hospital, D04 T6F4 Dublin, Ireland; (G.D.); (K.S.); (B.N.)
| | - Kieran Sheahan
- Centre for Colorectal Disease, St. Vincent’s University Hospital, D04 T6F4 Dublin, Ireland; (G.D.); (K.S.); (B.N.)
| | - Blathnaid Nolan
- Centre for Colorectal Disease, St. Vincent’s University Hospital, D04 T6F4 Dublin, Ireland; (G.D.); (K.S.); (B.N.)
| | - Pavel Vodicka
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, 121 08 Prague, Czech Republic; (L.V.); (V.V.); (P.V.)
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, 323 00 Pilsen, Czech Republic; (V.L.); (J.B.)
- Institute of Experimental Medicine ASCR, 142 20 Prague, Czech Republic;
| | - David J. Hughes
- Cancer Biology and Therapeutics Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland; (M.M.); (N.A.)
- Correspondence: ; Tel.: +353-1-716-6988
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11
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Liu Q, Du P, Zhu Y, Zhang X, Cai J, Zhang Z. Thioredoxin reductase 3 suppression promotes colitis and carcinogenesis via activating pyroptosis and necrosis. Cell Mol Life Sci 2022; 79:106. [PMID: 35094204 PMCID: PMC11072778 DOI: 10.1007/s00018-022-04155-y] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 01/01/2022] [Accepted: 01/17/2022] [Indexed: 01/06/2023]
Abstract
BACKGROUND Txnrd3 as selenoprotein plays key roles in antioxidant process and sperm maturation. Inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease, are becoming significantly increasing disease worldwide in recent years which are proved relative to diet, especially selenium intake. METHODS In the present study, 8-week-old C57BL/6N male Txnrd3-/-, Txnrd3-/ + , Txnrd3 + / + mice, weight 25-30 g, were randomly chosen and each group with 30 mice. Feed 3.5% DSS drinking water and normal water continuously for 7 days. Mouse colon cancer cells (CT26) were cultured in vitro to establish Txnrd3 overexpressed/knocked-down model by cell transfection technology. Morphology and ultrastructure, calcium levels, ROS level, cell death were observed and detected in vivo and vitro. RESULTS In Txnrd3-/-mice, ulcerative colitis was more severe, the morphological and ultrastructural lesions were also more prominent compared with wild-type mice, accompanied by the significantly increased expression of NLRP3, Caspase1, RIPK3, and MLKL. Overexpression of Txnrd3 could lead to increased oxidative stress through intracellular calcium outflow-induced oxidative stress increase followed by necrosis and pyroptosis pathway activation and further inhibit the growth and proliferation of colon cancer cells. CONCLUSION Txnrd3 overexpression leads to intracellular calcium outflow and increased ROS, which eventually leads to necrosis and focal death of colon cancer cells, while causing Txnrd3-/- mice depth of the crypt deeper, weakened intestinal secretion and immune function and aggravate the occurrence of ulcerative colitis. The present study lays a foundation for the prevention and treatment of ulcerative colitis and colon carcinoma in clinic treatment.
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Affiliation(s)
- Qi Liu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Pengyue Du
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Yue Zhu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Xintong Zhang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Jingzeng Cai
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Ziwei Zhang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China.
- Key Laboratory of the Provincial Education, Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin, 150030, People's Republic of China.
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12
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Mahmood MHR, Qayyum MA, Yaseen F, Farooq T, Farooq Z, Yaseen M, Irfan A, Muddassir K, Zafar MN, Qamar MT, Abbasi AM, Liu HY. Multivariate Investigation of Toxic and Essential Metals in the Serum from Various Types and Stages of Colorectal Cancer Patients. Biol Trace Elem Res 2022; 200:31-48. [PMID: 33635516 DOI: 10.1007/s12011-021-02632-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 02/08/2021] [Indexed: 01/22/2023]
Abstract
Colorectal cancer (CRC) is currently one of the most frequent malignant neoplasms, ranking 3rd in incidence and 2nd in mortality both in the USA and across the world. The pathogenesis of CRC is a complex interaction between genetic susceptibility and environmental factors such as exposure to metals. Therefore, the present study was intended to assess the imbalances in the concentrations of selected essential/toxic elements (Pb, Cr, Fe, Zn, As, Cd, Cu, Se, Ni, and Hg) in the serum of newly diagnosed colorectal carcinoma patients (n = 165) in comparison with counterpart controls (n = 151) by atomic absorption spectrometry after wet-acid digestion method. Serum carcinoembryonic antigen (CEA) of the CRC patients was determined using immunoradiometric method. Body mass index (BMI) which is an established risk factor for CRC was also calculated for patients and healthy controls. Conversely, average Ni (2.721 μg/g), Cd (0.563 μg/g), As (0.539 μg/g), and Pb (1.273 μg/g) levels were significantly elevated in the serum of CRC patients compared to the healthy donors, while the average Se (7.052 μg/g), Fe (15.67 μg/g), Cu (2.033 μg/g), and Zn (8.059 μg/g) concentrations were elevated in controls. The correlation coefficients between the elements in the cancerous patients demonstrated significantly dissimilar communal relationships compared with the healthy subjects. Significant differences in the elemental levels were also showed for CRC types (primary colorectal lymphoma, gastrointestinal stromal tumor, and adenocarcinoma) and CRC stages (stage-I, stage-II, stage-III, and stage-IV) among the patients. Majority of the elements demonstrated perceptible disparities in their levels based on dietary, habitat, gender, and smoking habits of the malignant patients and healthy subjects. Multivariate methods revealed noticeably divergent apportionment among the toxic/essential elements in the cancerous patients than the healthy counterparts. Overall, the study showed significantly divergent distribution and associations of the essential and toxic elemental levels in the serum of the CRC patients in comparison with the healthy donors.
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Affiliation(s)
- Mian H R Mahmood
- Department of Chemistry, Division of Science & Technology, University of Education, Lahore, Pakistan.
| | - Muhammad Abdul Qayyum
- Department of Chemistry, Division of Science & Technology, University of Education, Lahore, Pakistan
| | - Farhan Yaseen
- Department of Chemistry, Division of Science & Technology, University of Education, Lahore, Pakistan
| | - Tahir Farooq
- Department of Applied Chemistry, Government College University, Faisalabad, Pakistan
| | - Zahid Farooq
- Department of Physics, Division of Science & Technology, University of Education, Lahore, Pakistan
| | - Muhammad Yaseen
- Department of Chemistry, Division of Science & Technology, University of Education, Lahore, Pakistan
| | - Ahmad Irfan
- Research Center for Advanced Materials Science, King Khalid University, P.O. Box 9004, Abha, 61413, Saudi Arabia
- Department of Chemistry, Faculty of Science, King Khalid University, P.O. Box 9004, Abha, 61413, Saudi Arabia
| | - Khawaja Muddassir
- Division of Pulmonary Critical Care and Sleep Medicine, University of Tennessee Health Science Center, Memphis, TN, 38163, USA
| | | | - Muhammad Tariq Qamar
- Department of Chemistry, Forman Christian College (A Chartered University), Ferozepur Road, Lahore, 54600, Pakistan
| | - Arshad Mehmood Abbasi
- Department of Environmental Sciences, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, Pakistan
| | - Hai-Yang Liu
- Department of Chemistry, South China University of Technology, Guangzhou, 510641, China
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13
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Ye R, Huang J, Wang Z, Chen Y, Dong Y. Trace Element Selenium Effectively Alleviates Intestinal Diseases. Int J Mol Sci 2021; 22:ijms222111708. [PMID: 34769138 PMCID: PMC8584275 DOI: 10.3390/ijms222111708] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 10/18/2021] [Accepted: 10/26/2021] [Indexed: 12/28/2022] Open
Abstract
Selenium (Se) is an essential trace element in the body. It is mainly used in the body in the form of selenoproteins and has a variety of biological functions. Intestinal diseases caused by chronic inflammation are among the most important threats to human health, and there is no complete cure at present. Due to its excellent antioxidant function, Se has been proven to be effective in alleviating intestinal diseases such as inflammatory bowel diseases (IBDs). Therefore, this paper introduces the role of Se and selenoproteins in the intestinal tract and the mechanism of their involvement in the mediation of intestinal diseases. In addition, it introduces the advantages and disadvantages of nano-Se as a new Se preparation and traditional Se supplement in the prevention and treatment of intestinal diseases, so as to provide a reference for the further exploration of the interaction between selenium and intestinal health.
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Affiliation(s)
- Ruihua Ye
- College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; (R.Y.); (Z.W.); (Y.C.)
| | - Jiaqiang Huang
- Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, China Agricultural University, Beijing 100193, China;
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China
| | - Zixu Wang
- College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; (R.Y.); (Z.W.); (Y.C.)
| | - Yaoxing Chen
- College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; (R.Y.); (Z.W.); (Y.C.)
| | - Yulan Dong
- College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; (R.Y.); (Z.W.); (Y.C.)
- Correspondence:
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14
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Zhang L, Zhao Q, Mao L, Li H, Zhuang M, Wang J, Liu Y, Qi M, Du X, Xia Z, Sun N, Liu Q, Chen H, Zhang R. Bioinformatics Analyses Reveal the Prognostic Value and Biological Roles of SEPHS2 in Various Cancers. Int J Gen Med 2021; 14:6059-6076. [PMID: 34594130 PMCID: PMC8478514 DOI: 10.2147/ijgm.s328222] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 09/02/2021] [Indexed: 12/30/2022] Open
Abstract
Purpose Selenophosphate synthetase 2 (SEPHS2) has been shown to regulate selenoprotein biosynthesis by catalyzing the synthesis of active selenium donor selenophosphate. SEPHS2 influences the survival of tumor cells. However, few studies have explored the expression level and prognostic of SEPHS2 in various cancers. Methods The expression of SEPHS2 in human tumor tissues and normal adjacent tissues was analyzed in The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Human Protein Atlas (HPA), and UALCAN databases. Cox regression analysis and Kaplan–Meier curve analysis were performed to analyze the association of SEPHS2 expression with the prognosis of cancer patients. The expression and prognosis of SEPHS2 in gliomas were further verified using the Chinese Glioma Genome Atlas (CGGA) dataset. The relationship between SEPHS2 and immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), and neoantigens was comprehensively explored using a TCGA cohort. The mechanism by which SEPHS2 regulates tumor progression was explored by using the STRING database. A nomogram was constructed using the R software to predict the overall survival (OS) of patients with brain lower grade glioma (LGG). Results SEPHS2 was highly expressed in many cancers including LGG. Its high expression was significantly associated with poor OS, disease-free survival (DFS), and progression-free survival (PFS). Univariate and multivariate Cox analyses showed that SEPHS2 was an independent prognostic factor for LGG. Concordance index and calibration curves revealed that the nomogram had good predictive performance (concordance index: 0.791; 95% CI: 0.732–1). A significant correlation was found between SEPHS2 and immune infiltration, TMB, MSI, and tumor neoantigens across diverse cancers. Enrichment analysis showed that SEPHS2 may regulate the PPAR signaling pathway. Conclusion SEPHS2 expression regulates tumor development and it is a potential treatment target and prognostic biomarker, especially for lower grade glioma.
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Affiliation(s)
- Luyu Zhang
- School of Nursing, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People's Republic of China
| | - Qianqian Zhao
- School of Nursing, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People's Republic of China
| | - Leilei Mao
- School of Information Engineering, Chang'an University, Xi'an, Shaanxi, People's Republic of China
| | - Huanze Li
- School of Nursing, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People's Republic of China
| | - Miaoqing Zhuang
- School of Nursing, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People's Republic of China
| | - Jiayi Wang
- School of Nursing, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People's Republic of China
| | - Yue Liu
- School of Nursing, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People's Republic of China
| | - Meng Qi
- Ankang R & D Center of Se-enriched Products, Ankang, Shaanxi, People's Republic of China
| | - Xiaoping Du
- Ankang R & D Center of Se-enriched Products, Ankang, Shaanxi, People's Republic of China
| | - Zengrun Xia
- Ankang R & D Center of Se-enriched Products, Ankang, Shaanxi, People's Republic of China
| | - Na Sun
- School of Public Health, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People's Republic of China
| | - Qiling Liu
- School of Public Health, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People's Republic of China
| | - Hongfang Chen
- School of Nursing, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People's Republic of China.,Shaanxi Academy of Tradional Chinese Medicine, Xi'an, Shaanxi, People's Republic of China.,Shaanxi Provincial Hospital of Chinese Medicine, Xi'an, Shaanxi, People's Republic of China
| | - Rongqiang Zhang
- School of Public Health, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People's Republic of China
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15
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Schomburg L. Selenium Deficiency Due to Diet, Pregnancy, Severe Illness, or COVID-19-A Preventable Trigger for Autoimmune Disease. Int J Mol Sci 2021; 22:8532. [PMID: 34445238 PMCID: PMC8395178 DOI: 10.3390/ijms22168532] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 07/30/2021] [Accepted: 08/06/2021] [Indexed: 12/11/2022] Open
Abstract
The trace element selenium (Se) is an essential part of the human diet; moreover, increased health risks have been observed with Se deficiency. A sufficiently high Se status is a prerequisite for adequate immune response, and preventable endemic diseases are known from areas with Se deficiency. Biomarkers of Se status decline strongly in pregnancy, severe illness, or COVID-19, reaching critically low concentrations. Notably, these conditions are associated with an increased risk for autoimmune disease (AID). Positive effects on the immune system are observed with Se supplementation in pregnancy, autoimmune thyroid disease, and recovery from severe illness. However, some studies reported null results; the database is small, and randomized trials are sparse. The current need for research on the link between AID and Se deficiency is particularly obvious for rheumatoid arthritis and type 1 diabetes mellitus. Despite these gaps in knowledge, it seems timely to realize that severe Se deficiency may trigger AID in susceptible subjects. Improved dietary choices or supplemental Se are efficient ways to avoid severe Se deficiency, thereby decreasing AID risk and improving disease course. A personalized approach is needed in clinics and during therapy, while population-wide measures should be considered for areas with habitual low Se intake. Finland has been adding Se to its food chain for more than 35 years-a wise and commendable decision, according to today's knowledge. It is unfortunate that the health risks of Se deficiency are often neglected, while possible side effects of Se supplementation are exaggerated, leading to disregard for this safe and promising preventive and adjuvant treatment options. This is especially true in the follow-up situations of pregnancy, severe illness, or COVID-19, where massive Se deficiencies have developed and are associated with AID risk, long-lasting health impairments, and slow recovery.
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Affiliation(s)
- Lutz Schomburg
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Institut für Experimentelle Endokrinologie, Cardiovascular-Metabolic-Renal (CMR)-Research Center, Hessische Straße 3-4, Charitéplatz 1, 10117 Berlin, Germany
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16
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Wu W, Li D, Feng X, Zhao F, Li C, Zheng S, Lyu J. A pan-cancer study of selenoprotein genes as promising targets for cancer therapy. BMC Med Genomics 2021; 14:78. [PMID: 33706760 PMCID: PMC7948377 DOI: 10.1186/s12920-021-00930-1] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 02/26/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND The most important health benefit of selenium (Se) is in the prevention and control of cancer. Glutathione peroxidases (GPXs) and thioredoxin reductases (TXNRDs) are selenoenzymes that are thought to play a role in oxidative stress. The differential expression of genes of the TXNRD and GPX families is closely related to carcinogenesis and the occurrence of cancer. This study comprehensively analyzed the expression profiles of seven genes in the TXNRD and GPX families, in terms of their correlations with patient survival and immune-cell subtypes, tumor microenvironment, and drug sensitivity. RESULTS The expression profiles of genes in the TXNRD and GPX families differ between different types of cancer, and also between and within individual cancer cases. The expression levels of the seven analyzed genes are related to the overall survival of patients. The TXNRD1 and TXNRD3 genes are mainly related to poor prognoses, while other genes are related to good or poor prognoses depending on the type of cancer. All of the genes were found to be correlated to varying degrees with immune-cell subtypes, level of mechanistic cell infiltration, and tumor cell stemness. The TXNRD1, GPX1, and GPX2 genes may exert dual effects in tumor mutagenesis and development, while the TXNRD1, GPX1, GPX2, and GPX3 genes were found to be related to drug sensitivity or the formation of drug resistance. CONCLUSIONS The results will greatly help in identifying the association between genes and tumorigenesis, especially in the immune response, tumor microenvironment, and drug resistance, and very important when attempting to identify new therapeutic targets.
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Affiliation(s)
- Wentao Wu
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, 613 Whampoa Avenue, Tianhe District, Guangzhou, China
- School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China
| | - Daning Li
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, 613 Whampoa Avenue, Tianhe District, Guangzhou, China
- School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China
| | - Xiaojie Feng
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, 613 Whampoa Avenue, Tianhe District, Guangzhou, China
- School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China
| | - Fanfan Zhao
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, 613 Whampoa Avenue, Tianhe District, Guangzhou, China
- School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China
| | - Chengzhuo Li
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, 613 Whampoa Avenue, Tianhe District, Guangzhou, China
- School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China
| | - Shuai Zheng
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, 613 Whampoa Avenue, Tianhe District, Guangzhou, China
| | - Jun Lyu
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, 613 Whampoa Avenue, Tianhe District, Guangzhou, China.
- School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
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The Interaction between Dietary Selenium Intake and Genetics in Determining Cancer Risk and Outcome. Nutrients 2020; 12:nu12082424. [PMID: 32806741 PMCID: PMC7468715 DOI: 10.3390/nu12082424] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 08/05/2020] [Accepted: 08/07/2020] [Indexed: 02/06/2023] Open
Abstract
There is considerable interest in the trace element selenium as a possible cancer chemopreventive dietary component, but supplementation trials have not indicated a clear benefit. Selenium is a critical component of selenium-containing proteins, or selenoproteins. Members of this protein family contain selenium in the form of selenocysteine. Selenocysteine is encoded by an in-frame UGA codon recognized as a selenocysteine codon by a regulatory element, the selenocysteine insertion sequence (SECIS), in the 3′-untranslated region of selenoprotein mRNAs. Epidemiological studies have implicated several selenoprotein genes in cancer risk or outcome based on associations between allelic variations and disease risk or mortality. These polymorphisms can be found in or near the SECIS or in the selenoprotein coding sequence. These variations both function to control protein synthesis and impact the efficiency of protein synthesis in response to the levels of available selenium. Thus, an individual’s genetic makeup and nutritional intake of selenium may interact to predispose them to acquiring cancer or affect cancer progression to lethality.
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The Role of Selenium in Health and Disease: Emerging and Recurring Trends. Nutrients 2020; 12:nu12041049. [PMID: 32290296 PMCID: PMC7230933 DOI: 10.3390/nu12041049] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 04/06/2020] [Indexed: 02/06/2023] Open
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19
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Wang ST, Cui WQ, Pan D, Jiang M, Chang B, Sang LX. Tea polyphenols and their chemopreventive and therapeutic effects on colorectal cancer. World J Gastroenterol 2020; 26:562-597. [PMID: 32103869 PMCID: PMC7029350 DOI: 10.3748/wjg.v26.i6.562] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Revised: 12/30/2019] [Accepted: 01/11/2020] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC), a multifactorial disease, is usually induced and developed through complex mechanisms, including impact of diet and lifestyle, genomic abnormalities, change of signaling pathways, inflammatory response, oxidation stress, dysbiosis, and so on. As natural polyphenolic phytochemicals that exist primarily in tea, tea polyphenols (TPs) have been shown to have many clinical applications, especially as anticancer agents. Most animal studies and epidemiological studies have demonstrated that TPs can prevent and treat CRC. TPs can inhibit the growth and metastasis of CRC by exerting the anti-inflammatory, anti-oxidative or pro-oxidative, and pro-apoptotic effects, which are achieved by modulations at multiple levels. Many experiments have demonstrated that TPs can modulate several signaling pathways in cancer cells, including the mitogen-activated protein kinase pathway, phosphatidylinositol-3 kinase/Akt pathway, Wnt/β-catenin pathway, and 67 kDa laminin receptor pathway, to inhibit proliferation and promote cell apoptosis. In addition, novel studies have also suggested that TPs can prevent the growth and metastasis of CRC by modulating the composition of gut microbiota to improve immune system and decrease inflammatory responses. Molecular pathological epidemiology, a novel multidisciplinary investigation, has made great progress on CRC, and the further molecular pathological epidemiology research should be developed in the field of TPs and CRC. This review summarizes the existing in vitro and in vivo animal and human studies and potential mechanisms to examine the effects of tea polyphenols on CRC.
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Affiliation(s)
- Shi-Tong Wang
- Department of Cardiovascular Ultrasound, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Wen-Qi Cui
- Department of Neurology, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Dan Pan
- Department of Geriatrics, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Min Jiang
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Bing Chang
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Li-Xuan Sang
- Department of Geriatrics, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
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20
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Gibbs DC, Song M, McCullough ML, Um CY, Bostick RM, Wu K, Flanders WD, Giovannucci E, Jenab M, Brustad M, Tjønneland A, Perez-Cornago A, Trichopoulou A, Tsilidis KK, Hultdin J, Barricarte Gurrea A, Bueno-de-Mesquita B, Mahamat-Saleh Y, Kühn T, Gunter MJ, Weiderpass E, Fedirko V. Association of Circulating Vitamin D With Colorectal Cancer Depends on Vitamin D-Binding Protein Isoforms: A Pooled, Nested, Case-Control Study. JNCI Cancer Spectr 2020; 4:pkz083. [PMID: 32337495 PMCID: PMC7050153 DOI: 10.1093/jncics/pkz083] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Revised: 09/17/2019] [Accepted: 10/11/2019] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Higher circulating 25-hydroxyvitamin-D [25(OH)D] concentrations are consistently inversely associated with colorectal cancer (CRC) risk in observational studies. However, it is unknown whether this association depends on the functional GC-rs4588*A (Thr436Lys) variant encoding the vitamin D-binding protein-2 (DBP2) isoform, which may affect vitamin D status and bioavailability. METHODS We analyzed data from 1710 incident CRC cases and 1649 incidence-density-matched controls nested within three prospective cohorts of mostly Caucasians. Study-specific incidence rate ratios (RRs) for associations of prediagnostic, season-standardized 25(OH)D concentrations according to DBP2 isoform with CRC were estimated using multivariable unconditional logistic regression and were pooled using fixed-effects models. All statistical significance tests were two-sided. RESULTS The odds of having 25(OH)D concentrations less than 50 nmol/L (considered insufficient by the Institute of Medicine) were 43% higher for each DBP2-encoding variant (rs4588*A) inherited (per DBP2 odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.27 to 1.62, P trend = 1.2 × 10-8). The association of 25(OH)D concentrations with CRC risk differed by DBP2: 25(OH)D concentrations considered sufficient (≥ 50 nmol/L), relative to deficient (< 30 nmol/L), were associated with a 53% lower CRC risk among individuals with the DBP2 isoform (RR = 0.47, 95% CI = 0.33 to 0.67), but with a non-statistically significant 12% lower risk among individuals without it (RR = 0.88, 95% CI = 0.61 to 1.27) (P heterogeneity = .01). CONCLUSIONS Our results suggest that the 25(OH)D-CRC association may differ by DBP isoform, and those with a DBP2-encoding genotype linked to vitamin D insufficiency may particularly benefit from adequate 25(OH)D for CRC prevention.
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Affiliation(s)
- David Corley Gibbs
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA
| | - Mingyang Song
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
| | | | - Caroline Y Um
- Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA
| | - Roberd M Bostick
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA
- Winship Cancer Institute, Emory University, Atlanta, GA
| | - Kana Wu
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
| | - W Dana Flanders
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA
| | - Edward Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Mazda Jenab
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Magritt Brustad
- Department of Community Medicine, The Arctic University of Norway, Tromsø, Norway
| | - Anne Tjønneland
- Danish Cancer Society Research Center, Copenhagen, Denmark
- Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Aurora Perez-Cornago
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | | | - Konstantinos K Tsilidis
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | - Johan Hultdin
- Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
| | - Aurelio Barricarte Gurrea
- Navarra Public Health Institute, Pamplona, Spain
- Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
- CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain
| | - Bas Bueno-de-Mesquita
- Former Senior Scientist, Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
- Former Associate Professor, Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands
- Former Visiting Professor, Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, UK
- Former Visiting Professor, Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Yahya Mahamat-Saleh
- CESP, Faculty de médecine, University of Paris-Sud, Fac. de Médecine-UVSQ, INSERM, Université Paris-Saclay, Villejuif, France
- Institut Gustave Roussy, Villejuif, France
| | - Tilman Kühn
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Marc J Gunter
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | | | - Veronika Fedirko
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA
- Winship Cancer Institute, Emory University, Atlanta, GA
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21
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Leonardi A, Evke S, Lee M, Melendez JA, Begley TJ. Epitranscriptomic systems regulate the translation of reactive oxygen species detoxifying and disease linked selenoproteins. Free Radic Biol Med 2019; 143:573-593. [PMID: 31476365 PMCID: PMC7650020 DOI: 10.1016/j.freeradbiomed.2019.08.030] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 08/28/2019] [Accepted: 08/29/2019] [Indexed: 02/07/2023]
Abstract
Here we highlight the role of epitranscriptomic systems in post-transcriptional regulation, with a specific focus on RNA modifying writers required for the incorporation of the 21st amino acid selenocysteine during translation, and the pathologies linked to epitranscriptomic and selenoprotein defects. Epitranscriptomic marks in the form of enzyme-catalyzed modifications to RNA have been shown to be important signals regulating translation, with defects linked to altered development, intellectual impairment, and cancer. Modifications to rRNA, mRNA and tRNA can affect their structure and function, while the levels of these dynamic tRNA-specific epitranscriptomic marks are stress-regulated to control translation. The tRNA for selenocysteine contains five distinct epitranscriptomic marks and the ALKBH8 writer for the wobble uridine (U) has been shown to be vital for the translation of the glutathione peroxidase (GPX) and thioredoxin reductase (TRXR) family of selenoproteins. The reactive oxygen species (ROS) detoxifying selenocysteine containing proteins are a prime examples of how specialized translation can be regulated by specific tRNA modifications working in conjunction with distinct codon usage patterns, RNA binding proteins and specific 3' untranslated region (UTR) signals. We highlight the important role of selenoproteins in detoxifying ROS and provide details on how epitranscriptomic marks and selenoproteins can play key roles in and maintaining mitochondrial function and preventing disease.
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Affiliation(s)
- Andrea Leonardi
- Colleges of Nanoscale Science and Engineering, University at Albany, State University of New York, Albany, NY, USA
| | - Sara Evke
- Colleges of Nanoscale Science and Engineering, State University of New York Polytechnic Institute, Albany, NY, USA
| | - May Lee
- Colleges of Nanoscale Science and Engineering, State University of New York Polytechnic Institute, Albany, NY, USA
| | - J Andres Melendez
- Colleges of Nanoscale Science and Engineering, State University of New York Polytechnic Institute, Albany, NY, USA.
| | - Thomas J Begley
- Department of Biological Sciences, University at Albany, State University of New York, Albany, NY, USA; RNA Institute, University at Albany, State University of New York, Albany, NY, USA.
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