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MicroRNA-1322 regulates ECRG2 allele specifically and acts as a potential biomarker in patients with esophageal squamous cell carcinoma§

Authors

  • Tengfei Zhang,

    1. State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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  • Dan Zhao,

    1. State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
    Current affiliation:
    1. Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, Maryland, USA.
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  • Qiming Wang,

    1. Department of Internal Medicine, Henan Tumor Hospital, Zhengzhou University, Zhengzhou, China
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  • Xiying Yu,

    1. State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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  • Yaling Cui,

    1. Medical Record Library of Medical Services, Henan Tumor Hospital, Zhengzhou University, Zhengzhou, China
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  • Liping Guo,

    1. State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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  • Shih Hsin Lu

    Corresponding author
    1. State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
    • Department of Etiology and Carcinogenesis, Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Beijing 100021, China.
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  • Authorship: Tengfei Zhang and Dan Zhao performed microRNA-1322 related cell experiments, statistical and bioinformatics analysis and drafting of the manuscript; Qiming Wang helped with ESCC tissue and serum sample collection and processing; Xiying Yu provided quantitative RT-PCR of microRNA technical support; Yaling Cui in sample and clinical pathological data collection; Liping Guo in study supervision; Shih Hsin Lu conducted the study design.

  • Each author approved the final version of the manuscript.

  • §

    This project was approved by the Ethics Committee of Henan Tumor Hospital (Henan, China) on January 9th, 2008.

  • This work had taken a poster presentation (Poster session A23) in the “Ninth Annual International Conference on Frontiers in Cancer Prevention Research” (November 7–10, 2010, Philadelphia, USA) and got the Scholar-in-Training Award supported by Susan G. Komen for the Cure®.

Abstract

A short tandem repeat (STR) polymorphism in the 3′UTR region of esophageal cancer-related gene 2 (ECRG2, also known as SPINK7) has been widely reported to be associated with the incidence and the prognosis of esophageal squamous cell carcinoma (ESCC). This study explores how the microRNA binding to the STR region affects ECRG2 expression in ESCC. Dual-luciferase reporter assays were used to verify the effects of the four microRNAs (miR-580, miR-1182, miR-1272, and miR-1322) predicted to bind the STR region of the ECRG2 3′ untranslated region (UTR). The expression of identified effective microRNA was then analyzed in 44 paired ESCC and adjacent normal tissues and 402 case–controlled serum samples (divided into a discovery group and an independent validation group) by real-time RT-PCR assay. We found that only miR-1322 could significantly down-regulate the ECRG2 with TCA3 allele (P < 0.01), but it could not down-regulate the ECRG2 with TCA4 allele significantly (P > 0.05). MiR-1322 was also expressed significantly higher in ESCC tissue and serum samples than in controls (both P < 0.01). Additionally, serum levels of miR-1322 yielded an under receiver operating characteristic (ROC) curve area of 0.847 (95% CI, 0.795–0.890) for discriminating ESCCs from healthy controls in the discovery group and a similar result was obtained in the validation group (under ROC area is 0.845; 95%CI, 0.780–0.897). We conclude that miR-1322 can regulate ECRG2 in an allele-specific manner and that serum levels of miR-1322 can serve as a potential diagnostic biomarker for patients with ESCC. © 2012 Wiley Periodicals, Inc.

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