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Down-Regulation of PTEN Expression Modulated by Dysregulated miR-21 Contributes to the Progression of Esophageal Cancer

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Abstract

Background and Aim

miR-21, a putative tumor oncomiR, is a frequently overexpressed miRNA in a variety of tumors. Because it targets tumor-suppressor genes it has been linked to tumor progression. In this study we investigated the role of miR-21 in esophageal squamous cell carcinoma (ESCC), and its possible mechanism.

Methods

Expression of miR-21 was detected by stem–loop RT-PCR in tissue from 76 invasive ESCC at stage I–IV and in their corresponding para-cancerous histological normal tissues (PCHNT). Thirty endoscopic esophageal mucosal biopsy specimens from non-tumor patients were used as controls. Expression of PTEN in 76 paired ESCC and PCHNT was investigated by real-time RT-PCR and an immunohistochemical method, respectively. Paired tumor and PCHNT specimens of 20 ESCC cases were randomly selected for western blot analysis. The effect of miR-21 on PTEN expression was assessed in the ESCC cell line with an miR-21 inhibitor to reduce miR-21 expression. Furthermore, the roles of miR-21 in cell biology were analyzed by use of miR-21 inhibitor-transfected cells.

Results

Stem–loop RT-PCR revealed miR-21 was significantly overexpressed in ESCC tissues and cell lines. Overexpression of miR-21 correlated with tumor status, lymph node metastasis, and clinical stage. We demonstrated that knockdown of miR-21 significantly increased expression of PTEN protein. Consequent PTEN expression reduced cell proliferation, invasion, and migration.

Conclusions

Our findings suggest that miR-21 could be a potential oncomiR, probably by regulation of PTEN, and a novel prognostic factor for ESCC patients.

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Acknowledgments

This research was supported by a grant from the Program for New Century Excellent Talents in University, Ministry of Education, China (NCET-11-0949), a grant from the Science and Technology General Project of Zhejiang Province (no. 2009C33143), Key Research Projects of Medicine, Ministry of Health, China (no. WKJ2010-2-004), partly by a grant from the Backbone Talent of Zhejiang Provincial Medicine and Hygiene Platform Programs (no. 2011RCA009), a grant from the Scientific and Technological Innovations Fund of Henan Province Higher Education (no. 2009HAST1T001) and a grant from the Science and Technology Key Project of the Ministry of Education, China (no. 210130).

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Authors and Affiliations

  1. Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450052, People’s Republic of China

    Pei Li & Zi-Ming Dong

  2. Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, No. 38 Guangji Rd., Banshanqiao District, Hangzhou, 310022, People’s Republic of China

    Wei-Min Mao, Zhi-Guo Zheng & Zhi-Qiang Ling

  3. Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Hangzhou, People’s Republic of China

    Wei-Min Mao, Zhi-Guo Zheng & Zhi-Qiang Ling

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  1. Pei Li
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Correspondence to Pei Li or Zhi-Qiang Ling.

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Li, P., Mao, WM., Zheng, ZG. et al. Down-Regulation of PTEN Expression Modulated by Dysregulated miR-21 Contributes to the Progression of Esophageal Cancer. Dig Dis Sci 58, 3483–3493 (2013). https://doi.org/10.1007/s10620-013-2854-z

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  • DOI: https://doi.org/10.1007/s10620-013-2854-z

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