Genetic Variant of PP2A Subunit Gene Confers an Increased Risk of Primary Liver Cancer in Chinese

Wang, Youxin; Huang, Qingqing; Huang, Xinglei; Zhao, Hongda; Guan, Bin; Ban, Kechen; Zhu, Xuefeng; Ma, Zhixing; Tang, Yanmei; Su, Zhaohui; Nong, Qingqing

doi:10.2147/pgpm.s335555

Cited by 3 publications

(8 citation statements)

References 36 publications

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“… 20 , 21 A pond/ditch was defined as a water storage place, approximately 5–6 m in width, 100 m in length, and 1–2 m in depth, usually located close to residential areas. 6 Participants who had used water from ponds/ditches as the source of drinking water for 20 years or more were defined as drinkers of pond/ditch water. 6 This study was approved by the Medical Ethics Committee of Guangxi Medical University (GXMU-20160303-9), and the study was conducted in accordance with the Declaration of Helsinki.…”

Section: Methodsmentioning

confidence: 99%

“… 6 Participants who had used water from ponds/ditches as the source of drinking water for 20 years or more were defined as drinkers of pond/ditch water. 6 This study was approved by the Medical Ethics Committee of Guangxi Medical University (GXMU-20160303-9), and the study was conducted in accordance with the Declaration of Helsinki.…”

Section: Methodsmentioning

confidence: 99%

“…The experimental process of PBMCs isolation has been described in a previous study. 6 The PBMCs were treated with 3 μg/mL MC-LR (treated group) or medium alone (untreated group) for 24 h, and then the content of 8-OHdG was assayed by the kits obtained from Nanjing Jiancheng Biology Engineering Institute (Jiangsu, China). The exact 8-OHdG value of each participant was expressed as the 8-OHdG value of MC-LR-treated group minus the 8-OHdG value of the untreated group.…”

Section: Methodsmentioning

confidence: 99%

“…[3][4][5] HBV infection, exposure to aflatoxin B1 or microcystins (MCs)contaminated drinking water has been reported to contribute to the unusually high incidence of HCC in the Guangxi Province of China. 6,7 These factors can potentially modify the DNA structure and cause genomic instability, thus leading to a high risk of HCC. 8,9 Efficient and accurate repairs of DNA damage could maintain the stability of the genome.…”

Section: Introductionmentioning

confidence: 99%

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The Glu69Asp Polymorphism of EME1 Gene is Associated with an Increased Risk of Hepatocellular Carcinoma in Guangxi Population, China

Wang¹,

Huang²,

Su³

et al. 2022

IJGM

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Background The dysfunction of Essential meiotic endonuclease 1 homolog 1 (EME1) can lead to genomic instability and tumorigenesis. Single nucleotide polymorphisms (SNPs) in the EME1 gene have been reported to be associated with the risk of several cancers, but its association with hepatocellular carcinoma (HCC) has not been investigated. This study aimed to determine the association between EME1 SNPs and the risk of HCC. Methods This study included 645 HCC patients and 649 healthy controls from a Guangxi population of Southern China, and genotyped three functional SNPs (Glu69Asp: rs3760413A>C, Ile350Thr: rs12450550T>C, and rs11868055A>G) of the EME1 gene utilizing the Agena MassARRAY platform. Results The rs3760413C variant genotypes (AC+CC: Glu/Asp+Asp/Asp) conferred a 1.419-fold risk of HCC compared to the AA (Glu/Glu) genotype (adjusted OR = 1.419, 95% CI = 1.017–1.980), and the allele C increased the risk of HCC in a dose-dependent manner ( P trend = 0.017). Moreover, the effects of the rs3760413C variant genotypes were more pronounced in individuals who drank pond/ditch water (adjusted OR = 3.956, 95% CI = 1.413–11.076) than in those who never drank ( P = 0.033). We further observed that a potential carcinogen microcystin-LR induced more DNA oxidative damages in peripheral blood mononuclear cells from the carriers of rs3760413C variant genotypes than those from the subjects with AA genotype ( P = 0.006). A nomogram was also constructed combining the rs3760413A>C polymorphism and environmental risk factors for predicting HCC risk with a good discriminatory ability (concordance index = 0.892, 95% CI: 0.874–0.911) and good calibration (mean absolute error = 0.005). Conclusion Our data suggest that the Glu69Asp missense polymorphism (rs3760413) of EME1 gene is associated with the risk of HCC, which may be a susceptible biomarker of HCC in the Guangxi population.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Glu69Asp Polymorphism of EME1 Gene is Associated with an Increased Risk of Hepatocellular Carcinoma in Guangxi Population, China

Wang¹,

Huang²,

Su³

et al. 2022

IJGM

View full text Add to dashboard Cite

show abstract

“…A survey of 134 lakes in New Zealand found that the highest concentration of microcystins was 6.4 μg/L [ 20 ]. In 29 pond/ditch drinking water samples collected in Nanning District, Guangxi, China, the average MC-LR concentration was 0.5 μg/L [ 21 ]. The microcystin content was 13.38 μg/L, and the highest concentration was 35.8 μg/L in Lake Taihu of China after the collapse of cyanobacterial blooms, which greatly exceeded the WHO standard of 1 μg/L [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Gill Junction Injury and Microbial Disorders Induced by Microcystin-Leucine Arginine in Lithobates catesbeianus Tadpoles

Jiang

Wang

et al. 2022

Toxins

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Microcystin-LR (MC-LR) is widely present in waters around the world, but its potential toxic effects and mechanisms on amphibian gills remain unknown. In the present study, tadpoles (Lithobates catesbeianus) were exposed to environmentally realistic concentrations of 0.5, 2 μg/L MC-LR, and 0 μg/L MC-LR (Control) for 30 days with the objective to unveil the impairment of gill health. The lysozyme was downregulated, while pattern recognition receptors and complement and adaptive immune processes were upregulated and the ability of gill supernatant to inhibit pathogenic bacteria decreased in the 0.5 and 2 μg/L MC-LR groups. The transcriptions of epithelial barrier components (e.g., CLDN1) were significantly decreased in MC-LR-exposed gills, while the gill content of lipopolysaccharide (LPS) endotoxins and the transcriptions of downstream responsive genes (e.g., TLR4 and NF-κB) were concurrently increased. In addition, the number of eosinophils and the expression of pro-inflammatory cytokines (e.g., IL-1β and TNF-α) were increased. These results imply that exposure of tadpoles to low environmentally concentrations of MC-LR leads to inflammation, increased permeability, and a reduced ability to inhibit pathogenic bacteria. The epithelial cells of inner gill filaments increased and transcriptions of hypoxic stress genes (e.g., HIF-1α, FLT1, and SERPINE1) were upregulated within the exposed group. As a consequence, exposure to MC-LR may lead to hypoxic stress. MC-LR exposure also drove gill microbiota to a dysbiosis. The relative abundance of Elizabethkingia was positively correlated with content of LPS and transcriptions of NF-κB and TNF-α. Overall, this study presents the first evidence about the pronounced impacts of MC-LR exposure on gills of amphibians, highlighting the susceptibility of early developing tadpoles to the environmental risks of MC-LR.

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Downregulation of LncRNA GCLC-1 Promotes Microcystin-LR-Induced Malignant Transformation of Human Liver Cells by Regulating GCLC Expression

Huang

et al. 2023

Toxics

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Microcystin-LR (MCLR) is an aquatic toxin, which could lead to the development of hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) are considered important regulatory elements in the occurrence and development of cancer. However, the roles and mechanisms of lncRNAs during the process of HCC, induced by MCLR, remain elusive. Here, we identified a novel lncRNA, namely lnc-GCLC-1 (lncGCLC), which is in close proximity to the chromosome location of glutamate–cysteine ligase catalytic subunit (GCLC). We then investigated the role of lncGCLC in MCLR-induced malignant transformation of WRL68, a human hepatic cell line. During MCLR-induced cell transformation, the expression of lncGCLC and GCLC decreased continuously, accompanied with a consistently high expression of miR-122-5p. Knockdown of lncGCLC promoted cell proliferation, migration and invasion, but reduced cell apoptosis. A xenograft nude mouse model demonstrated that knockdown of lncGCLC promoted tumor growth. Furthermore, knockdown of lncGCLC significantly upregulated miR-122-5p expression, suppressed GCLC expression and GSH levels, and enhanced oxidative DNA damages. More importantly, the expression of lncGCLC in human HCC tissues was significantly downregulated in the high-microcystin exposure group, and positively associated with GCLC level in HCC tissues. Together, these findings suggest that lncGCLC plays an anti-oncogenic role in MCLR-induced malignant transformation, by regulating GCLC expression.

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Genetic Variant of PP2A Subunit Gene Confers an Increased Risk of Primary Liver Cancer in Chinese

Cited by 3 publications

References 36 publications

The Glu69Asp Polymorphism of EME1 Gene is Associated with an Increased Risk of Hepatocellular Carcinoma in Guangxi Population, China

The Glu69Asp Polymorphism of EME1 Gene is Associated with an Increased Risk of Hepatocellular Carcinoma in Guangxi Population, China

Gill Junction Injury and Microbial Disorders Induced by Microcystin-Leucine Arginine in Lithobates catesbeianus Tadpoles

Downregulation of LncRNA GCLC-1 Promotes Microcystin-LR-Induced Malignant Transformation of Human Liver Cells by Regulating GCLC Expression

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