Functional Polymorphisms in<i> IRAKs</i> Are Related to Hepatocellular Carcinoma Risk in Chinese Population

Wang, Hui; Song, Ci; Qi, Qi; Huang, Tingpei; Wang, Limin; Chen, Jianguo; Zhu, Jian; Hu, Zhibin; Dai, Juncheng

doi:10.1155/2018/1252849

Cited by 5 publications

(11 citation statements)

References 16 publications

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“…The data revealed that the A allele was prone to interfere with the production of IL‐6 and patients with this allele were more likely to suffer from severe EV71 infection. A previous study 15 indicated that the plausibility of reduced proinflammatory and increased proliferation rate of cells could be attributed to the unbalanced immunity reaction induced by rs4251545 in HCC. IL‐6 levels and the ratio of IL‐6/NF‐κB were much higher in severe cases than in mild cases but were lower in GA + AA genotypes than in GG genotypes among severe cases.…”

Section: Discussionmentioning

confidence: 99%

“…These results suggest that the polymorphism of rs4251545 in IRAK4 is involved in the pathogenesis of severe EV71 infection. Wang et al 15 pointed out that the A allele is positively associated with the risk of HBV-related HCC because the A allele reduced IRAK4 expression in the liver and increased the proliferation rate of L02 cells. Jun et al 22 also indicated that the rs4251545 A allele is associated with severe sepsis.…”

Section: Discussionmentioning

confidence: 99%

“…It is widely known that the host genetic background is related to the occurrence and development of diseases. Studies have shown that the IRAK4 polymorphism rs4251545 is related to several diseases, such as severe sepsis, hepatocellular carcinoma (HCC), and breast cancer 14–16 . Rs4251545 changes the G allele to the A allele in the 11th exon of IRAK4 , which causes an alanine‐to‐threonine substitution at amino acid 428 in the IRAK4 protein.…”

Section: Introductionmentioning

confidence: 99%

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Association of the IRAK4 rs4251545 genetic polymorphism with severity of enterovirus‐71 infection in Chinese children

Liu

Guo

et al. 2022

Immunity Inflam & Disease

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Introduction: This study aimed to explore the association between the IRAK4 polymorphism rs4251545 and the severity of enterovirus 71 (EV71) infection in Chinese children. Methods: We analyzed the IRAK4 polymorphism rs4251545 in 617 EV71infected patients and 410 controls using the improved multiplex ligation detection reaction. IRAK4 mRNA expression was tested by qRT-PCR. Serum concentrations of IL-6 and NF-κB were detected using ELISA. Results:The frequencies of the GA + AA genotype and A allele in the mild EV71 infection group and in the severe EV71 infection group were significantly higher than those in the normal control group. The frequency of the GA + AA genotype and A allele in severely infected EV71 patients was markedly higher than that in mildly infected EV71 patients. IRAK4 mRNA expression in mildly infected EV71 patients and severely infected patients was significantly higher than that in the control group. IRAK4 mRNA expression in GA + AA genotypes in both mild and severe EV71 infection groups was significantly higher than that in patients with the GG genotype. IL-6 concentration and the ratio of IL-6/NF-κB in severe EV71 cases were significantly lower in patients with the GA + AA genotype than in those with the GG genotype. The ratio of IL-6/NF-κB was distinctly higher in severely infected EV71 patients than in mildly infected and control subjects. Conclusions: The IRAK4 polymorphism rs4251545 was associated with the susceptibility and severity of EV71 infection. The A allele is a susceptible factor in the development of severe EV71 infection in Chinese children.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of the IRAK4 rs4251545 genetic polymorphism with severity of enterovirus‐71 infection in Chinese children

Liu

Guo

et al. 2022

Immunity Inflam & Disease

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“…The IRAKs (subtypes 1–4) are serine-threonine kinases involved in toll-like receptor and interleukin-1 signaling pathways, through which they regulate innate immunity and inflammation [ 50 ]. The rs4251545 polymorphisms of IRAK4 (p.Ala428Thr) were reported to modify susceptibility to hepatitis B virus (HBV)-related HCC via increased proliferation and reduced production of inflammatory cytokines and chemokines [ 51 ]. Further, IRAK1 augmented HCC cell stemness and drug resistance via AP-1/AKR1B10 signaling [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Long Noncoding RNAs Coregulated by Annexin A7 and JNK in Hepatocellular Carcinoma Cells Identified by Whole-Genome Expression Profiling

Deng

Jin

2020

BioMed Research International

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Knockdown of Annexin A7 (ANXA7) or C-Jun N-terminal kinase (JNK) inhibits the proliferation, migration, invasion, and lymphatic adhesion of hepatocellular carcinoma (HCC) cells, suggesting that ANXA7 and JNK signaling pathways contribute to HCC growth and lymph node metastasis (LNM). While the intervening molecular pathways are largely unknown, emerging evidence suggests that long noncoding RNAs (lncRNAs) participate in ANXA7 and JNK signaling. To identify potential therapeutic targets for HCC, we screened for lncRNAs differentially expressed among Hca-P cells stably expressing shRNA-ANXA7, shRNA-JNK, or control-shRNA. RNA sequencing identified 216 lncRNAs differentially expressed between shRNA-ANXA7 and control-shRNA cells, of which 101 were downregulated and 115 upregulated, as well as 436 lncRNAs differentially expressed between shRNA-JNK and control-shRNA cells, of which 236 were downregulated and 200 upregulated. Fifty-six lncRNAs were differentially expressed under both ANXA7 and JNK knockdown. We selected 4 of these for verification based on putative involvement in cancer regulation according to GO and KEEG analyses of target genes. Knockdown of ANXA7 or JNK suppressed expression of NONMMUT012084.2, NONMMUT024756.2, and ENSMUST00000130486, and enhanced expression of ENSMUST00000197932. These lncRNAs are intriguing candidate targets for mechanistic analysis of HCC progression and therapeutic intervention.

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“…Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, with high morbidity and mortality rates [1] and it is the second leading cause of cancer death [2]. The incidence of HCC in China accounts for almost half of the global incidence of HCC [3]. Statistics show that China accounts for half of the world’s new cases of and deaths due to HCC [4].…”

Section: Introductionmentioning

confidence: 99%

Upregulation of Long Non-Coding RNA ENST00000429227.1 Is Correlated with Poor Prognosis in Human Hepatocellular Carcinoma

Zhao

Kong

et al. 2019

Med Sci Monit

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BackgroundLong non-coding RNAs (lncRNAs) have been shown to play an important regulatory role in many tumors. This study was designed to investigate the expression of lncRNA ENST00000429227.1 in hepatocellular carcinoma (HCC) and to determine whether the expression of lncRNA ENST00000429227.1 affects the prognosis of HCC.Material/MethodslncRNA ENST00000429227.1 showing differences in expression between M1 and M2 was screened by microarray expression measurements. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of lncRNA ENST00000429227.1 in 161 HCC patients. The chi-square test was used to evaluate the relationship between the expression of ENST00000429227.1 and clinicopathological parameters. A survival curve was drawn and analyzed by Kaplan-Meier method. Cox regression was used for univariate and multivariate analysis to determine whether lncRNA ENST00000429227.1 is an independent factor of the occurrence and prognosis of HCC.ResultsA total of 3703 differentially expressed lncRNAs were obtained, of which 1777 were upregulated and 1926 were downregulated, with multiple change >1.5. The expression of lncRNA ENST00000429227.1 was upregulated in M2 cells. The expression of lncRNA ENST00000429227.1 in HCC tissues was higher than that in adjacent normal tissues (p<0.05), which was correlated with pathological parameters such as surgical margin (p=0.042), AFP (p=0.022) and Barcelona Clinic Liver Cancer (BCLC) stage (p=0.008). Survival analysis showed that high expression of lncRNA ENST00000429227.1 was associated with a decrease in overall survival (OS) rate of HCC patients. Cox regression analysis showed that high expression of ENST00000429227.1 may be an independent risk factor affecting the prognosis of HCC patients.ConclusionsThe results suggest that upregulation of ENST00000429227.1 is associated with poor prognosis of HCC patients, and may be a new biomarker for the diagnosis of HCC.

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Functional Polymorphisms in IRAKs Are Related to Hepatocellular Carcinoma Risk in Chinese Population

Cited by 5 publications

References 16 publications

Association of the IRAK4 rs4251545 genetic polymorphism with severity of enterovirus‐71 infection in Chinese children

Association of the IRAK4 rs4251545 genetic polymorphism with severity of enterovirus‐71 infection in Chinese children

Long Noncoding RNAs Coregulated by Annexin A7 and JNK in Hepatocellular Carcinoma Cells Identified by Whole-Genome Expression Profiling

Upregulation of Long Non-Coding RNA ENST00000429227.1 Is Correlated with Poor Prognosis in Human Hepatocellular Carcinoma

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