Oncotarget

Research Papers:

A single nucleotide polymorphism in the 3’-UTR of STAT3 regulates its expression and reduces risk of pancreatic cancer in a Chinese population

Beibei Zhu, Ying Zhu, Jiao Lou, Juntao Ke, Yi Zhang, Jiaoyuan Li, Yajie Gong, Yang Yang, Jianbo Tian, Xiating Peng, Danyi Zou, Rong Zhong, Jing Gong, Jiang Chang, Lu Li and Xiaoping Miao _

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Oncotarget. 2016; 7:62305-62311. https://doi.org/10.18632/oncotarget.11607

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Abstract

Beibei Zhu1,*, Ying Zhu1,*, Jiao Lou1, Juntao Ke1, Yi Zhang1, Jiaoyuan Li1, Yajie Gong1, Yang Yang1, Jianbo Tian1, Xiating Peng1, Danyi Zou1, Rong Zhong1, Jing Gong1, Jiang Chang1, Lu Li1,2, Xiaoping Miao1

1State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

2Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, China

*These authors contributed equally to this work

Correspondence to:

Lu Li, email: [email protected]

Xiaoping Miao, email: [email protected]

Keywords: pancreatic cancer, STAT3, genetic variants, susceptibility, case-control study

Received: May 06, 2016     Accepted: August 11, 2016     Published: August 25, 2016

ABSTRACT

Pancreatic cancer (PC) is one of the deadliest solid malignancies carrying a gloomy 5-year survival rate less than 5%. The signal transducer and activator of transcription 3 (STAT3) is a common transcriptional regulator, whose aberrant expression has been widely found in human cancers, including PC. Our current study aimed to illustrate the roles of common variants, in the three prime untranslated region (3’UTR) of STAT3, in modifying the risk of PC through two-stage case-control studies integrating biological experiments. We first explored the associations between two common variants (rs1053004 and rs1053005) and PC risk in 774 PC cases and 777 controls. Only rs1053004 T > C showed a significant association with a reduced risk of PC with an odds ratio (OR) and 95% confidence interval (CI) of 0.85 (0.74–0.98). Then we attempted to validate the association in another 940 cases and 1398 controls, and the significant association persisted with OR (95%CI) of 0.86 (0.76–0.97). Dual luciferase reporter gene assays indicated that C allele conferred a higher expression of STAT3 in three PC cell lines including Panc-1 (P = 3.0 × 10−3), BxPC-3 (P = 6.7 × 10−5) and SW1990 (P = 4.0 × 10−3). In conclusion, the current study provided evidence that rs1053004 T > C in 3’UTR of STAT3 may decrease the risk of PC through up-regulating the gene expression.


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