Ling Zhang

Publications (2)5.3 Total impact

• Article: Methylation-mediated repression of microRNA 129-2 enhances oncogenic SOX4 expression in HCC.

  Xiangmei Chen, Ling Zhang, Ting Zhang, Meili Hao, Xiaolei Zhang, Jiangbo Zhang, Qing Xie, Yongfeng Wang, Mingzhou Guo, Hui Zhuang, Fengmin Lu
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  ABSTRACT: Aberration of miR-129-2 has been linked to a variety of human tumours. However, whether miR-129-2 is involved in hepatocarcinogenesis remains unknown. Here, we investigate the involvement of miR-129-2 in HBV infection-related HCC. A total of 75 paired tumour and their corresponding non-tumour liver tissues from HCC patients with serum HBsAg positive were collected. The methylation of miR-129-2 gene was quantitatively analysed by a DNA methylation-sensitive endonuclease digestion followed by quantitative PCR. The expression of mature miR-129-2 (miR-129-3p) was detected by Taqman RT-PCR. SOX4 expression was detected using quantitative realtime RT-PCR, western blot and immunohistochemical staining. The function of miR-129-2 was investigated using cell proliferation and clonogenicity assays in vitro. Compared with the adjacent non-tumour tissues, tumour tissues exhibited significantly increased miR-129-2 hypermethylation both in frequency (37.33% vs. 8%, P < 0.0001) and in intensity (14.77% vs. 3.08%, P = 0.002). Accordantly, miR-129-3p expression in HCC tissues was significantly lower than that in non-tumour tissues (P = 0.0461), in a manner reversely correlated with the level of miR-129-2 hypermethylation. Notably, SOX4 level in the HCC tissues was significantly higher than that in non-tumour tissues (P = 0.0174) and normal liver tissues (P = 0.0077), correlated reversely with miR-129-3p level (P = 0.0105). Furthermore, overexpression of miR-129-2 in HepG2 reduced cell proliferation and clonogenicity, while co-expression with SOX4 could partially reverse its antitumor effects. In addition, SOX4 in HepG2 cell can enhance β-catenin/TCF activity by increasing β-catenin level. The current data indicated that methylation-mediated repression of miR-129-2 may enhance oncogenic SOX4 expression and involve in HCC tumorigenesis.
  Liver international: official journal of the International Association for the Study of the Liver 03/2013; 33(3):476-86. · 3.82 Impact Factor
• Article: Association of TNF-alpha genetic polymorphisms with hepatocellular carcinoma susceptibility: a case-control study in a Han Chinese population.

  Xiangmei Chen, Ling Zhang, Yibin Chang, Tao Shen, Ling Wang, Hui Zhuang, Fengmin Lu
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  ABSTRACT: The single nucleotide polymorphisms (SNPs) within the tumor necrosis factor-a (TNF-a) gene promoter region have been reported to be associated with susceptibility to various types of cancers. A case-control study (126 hepatocellular carcinoma [HCC] patients and 126 normal controls) was conducted to elucidate their possible association with the risk of hepatitis B virus (HBV)-related HCC in a Han Chinese population. TNF-alpha polymorphisms -1031T/C, -863C/A, -857C/T, -308G/A, and -238G/A were genotyped by polymerase chain reaction (PCR) and direct DNA sequencing. Disease associations were analyzed by the chi-square test or Fisher's exact test. When analyzed by overall groups, no significant differences in genotype and allele distributions were observed between the control and cases. However, stratified analysis according to sex showed that the frequency of the homozygous C allele of the -857 polymorphism was lower in female cases than in female controls (62.9% vs. 88.9%, p=0.026). In addition, further haplotype analysis revealed that the TCCGA (-1031/-863/-857/-308/-238) was more frequent in controls than cases (p=0.018; odds ratio = 0.266; 95% confidence interval, 0.083-0.857). These results indicated that the TNF-alpha-857C/T polymorphism may modify HBV-related HCC risk among women, and the haplotype TCCGA (-1031/-863/-857/-308/-238) may account for a decreased susceptibility to HCC development in the Han Chinese population. Additional studies in patients with different ethnic backgrounds are needed to validate these finding and to further explore the genetic pathogenesis of HBV-related HCC.
  The International journal of biological markers 07/2011; 26(3):181-187. · 1.48 Impact Factor