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A functional variant at miR-34a binding site in toll-like receptor 4 gene alters susceptibility to hepatocellular carcinoma in a Chinese Han population

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Tumor Biology

Abstract

Toll-like receptor 4 (TLR4) plays a key role in prompting the innate or immediate response. A growing body of evidence suggests that genetic variants of TLR4 gene were associated with the development of cancers. This study aimed to investigate the relationship of a functional variant (rs1057317) at microRNA-34a (miR-34a) binding site in toll-like receptor 4 gene and the risk of hepatocellular carcinoma. A single center-based case–control study was conducted. In this study, the polymerase chain reaction (PCR) and direct sequencing were used to genotype sequence variants of TLR4 in 426 hepatocellular carcinoma cases and 438 controls. The modification of rs1057317 on the binding of hsa-miR-34a to TLR4 messenger RNA (mRNA) was measured by luciferase activity assay. Individuals carrying the AA genotypes for the rs1057317 were associated significantly with increased risk of hepatocellular carcinoma comparing with those carrying wild-type homozygous CC genotypes (adjusted odds ratio [OR] by sex and age, from 1.116 to 2.452, P = 0.013). The activity of the reporter vector was lower in the reporter vector carrying C allele than the reporter vector carrying A allele. Furthermore, the expression of TLR4 was detected in the peripheral blood mononucleated cell of hepatocellular carcinoma (HCC) patients, suggesting that mRNA and protein levels of TLR4 might be associated with SNP rs1057317. Collectively, these results suggested that the risk of hepatocellular carcinoma was associated with a functional variant at miR-34a binding site in toll-like receptor 4 gene. miR-34a/TLR4 axis may play an important role in the development of hepatocellular carcinoma.

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Authors and Affiliations

  1. Department of Infectious Diseases, The First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, China

    Zi-Cheng Jiang & Ying-Ren Zhao

  2. Department of Infectious Diseases, Ankang City Central Hospital, Ankang, China

    Zi-Cheng Jiang

  3. Department of Infectious Diseases, Hanzhong Central Hospital, Hanzhong, China

    Xian-Mei Tang

  4. Department of Oncology, The Taixing People’s Hospital, Taixing, China

    Lei Zheng

Authors
  1. Zi-Cheng Jiang
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  2. Xian-Mei Tang
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  3. Ying-Ren Zhao
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  4. Lei Zheng
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Corresponding author

Correspondence to Lei Zheng.

Additional information

Zicheng Jiang and Xian-Mei Tang contributed equally to this article and should be considered co-first authors.

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Jiang, ZC., Tang, XM., Zhao, YR. et al. A functional variant at miR-34a binding site in toll-like receptor 4 gene alters susceptibility to hepatocellular carcinoma in a Chinese Han population. Tumor Biol. 35, 12345–12352 (2014). https://doi.org/10.1007/s13277-014-2547-z

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  • DOI: https://doi.org/10.1007/s13277-014-2547-z

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