Functional short tandem repeat polymorphism of PTPN11 and susceptibility to hepatocellular carcinoma in Chinese populations.
Functional short tandem repeat polymorphism of PTPN11 and susceptibility to hepatocellular carcinoma in Chinese populations.
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PTPN11功能性短串联重复多态性与中国人群肝癌易感性
DOI：
10.1371/journal.pone.0106841
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Gao Y
中科院分区：
文献类型：
--
作者：
Zhao X;Hu S;Wang L;Zhang Q;Zhu X;Zhao H;Wang C;Tao R;Guo S;Wang J;Xu J;He Y;Gao Y
背景：PTPN11编码酪氨酸磷酸酶Shp2，是调节细胞对激素和细胞因子反应的关键基因。Shp2的缺失促进了肝细胞癌的发生，提示PTPN11在肝细胞癌的发生中起着肿瘤抑制因子的作用。本研究旨在探讨PTPN11基因3‘非编码区短串联重复序列(STR)多态(Rs199618935)对中国人群肝癌易感性的影响。方法/主要研究结果我们分析了来自江苏中国的400例患者的相关性，并验证了来自上海的305例中国患者的研究结果。采用非条件Logistic回归分析rs199618935与肝癌风险的关系。进一步的生化研究和电子计算机研究被用来评估这种多态可能的功能意义。Logistic回归分析显示，与携带较短等位基因(11和12重复)的个体相比，携带较长等位基因(13和14重复)的个体患肝癌的风险显著降低[调整优势比(OR) = 0.6 3，95%可信区间(CI) = 0.5 3~0.76，P = 2.0 0×10−7]，携带15和16等位基因的个体患肝癌的风险进一步降低(调整OR = 0.46，95%CI = 0.34~0.62，P = 1.0 0×10−7)。生化研究表明，rs199618935的较长等位基因在体内和体外均有较高的PTPN11表达。报告基因系统中荧光素酶活性的改变提示STR对PTPN11表达的调控可能是一种转录事件。电子计算机预测表明，rs199618935的不同等位基因可以改变PTPN11基因的局部结构。结论/意义综合考虑，我们的研究结果提示，PTPN11内的STR多态可能通过影响PTPN11的表达而参与肝癌的发生。需要重复我们的研究和进一步的功能研究来验证我们的发现。
Background PTPN11, which encodes tyrosine phosphatase Shp2, is a critical gene mediating cellular responses to hormones and cytokines. Loss of Shp2 promotes hepatocellular carcinoma (HCC), suggesting that PTPN11 functions as a tumor suppressor in HCC tumorgenesis. The aim of this study was to evaluate the effects of the short tandem repeat (STR) polymorphism (rs199618935) within 3'UTR of PTPN11 on HCC susceptibility in Chinese populations. Methodology/Principal Findings We analyzed the associations in 400 patients from Jiangsu province of China, validating the findings in an additional 305 patients from Shanghai of China. Unconditional logistic regression was used to analyze the association between rs199618935 and HCC risk. Additional biochemical investigations and in-silico studies were used to evaluate the possible functional significance of this polymorphism. Logistic regression analysis showed that compared with individuals carrying shorter alleles (11 and 12 repeats), those subjects who carry longer alleles (13 and 14 repeats) had a significantly decreased risk of HCC [adjusted odds ratio (OR) = 0.63, 95% confidence interval (CI) = 0.53–0.76, P = 2.00×10−7], with the risk decreased even further in those carrying allele 15 and 16 (adjusted OR = 0.46, 95% CI = 0.34–0.62, P = 1.00×10−7). Biochemical investigations showed that longer alleles of rs199618935 conferred higher PTPN11 expression in vivo and in vitro. The altered luciferase activities in reporter gene system suggested that STR regulation of PTPN11 expression could be a transcriptional event. Finally, in-silico prediction revealed that different alleles of rs199618935 could alter the local structure of PTPN11 mRNA. Conclusions/Significance Taken together, our findings suggested that the STR polymorphism within PTPN11 contributes to hepatocarcinogenesis, possibly by affecting PTPN11 expression through a structure-dependent mechanism. The replication of our studies and further functional studies are needed to validate our findings.
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影响因子：
29.4
作者：
El-Serag HB
通讯作者：
El-Serag HB
影响因子：
50.3
作者：
Taylor BS;Schultz N;Hieronymus H;Gopalan A;Xiao Y;Carver BS;Arora VK;Kaushik P;Cerami E;Reva B;Antipin Y;Mitsiades N;Landers T;Dolgalev I;Major JE;Wilson M;Socci ND;Lash AE;Heguy A;Eastham JA;Scher HI;Reuter VE;Scardino PT;Sander C;Sawyers CL;Gerald WL
通讯作者：
Gerald WL
影响因子：
30.8
作者：
Kumar, Vinod;Kato, Naoya;Matsuda, Koichi
通讯作者：
Matsuda, Koichi
DOI：
10.1007/s00432-011-1143-5
发表时间：
2012-04-01
影响因子：
3.6
作者：
Jiang, Chengying;Hu, Fangke;Wei, Lixin
通讯作者：
Wei, Lixin
影响因子：
4.7
作者：
He, Caiyun;Tu, Huakang;Yuan, Yuan
通讯作者：
Yuan, Yuan