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JMJD1A promotes tumorigenesis and forms a feedback loop with EZH2/let-7c in NSCLC cells

  • Original Article
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Tumor Biology

Abstract

Lung cancer is the most common cause of cancer-related deaths worldwide, and non-small cell lung cancer (NSCLC) accounts for 80 to 85 % of all lung cancer. Although the standard treatment regimen has been established, long-term survival for NSCLC patients is still generally poor. The histone demethylase Jumonji domain containing 1A (JMJD1A) has been proposed as an oncogene in several types of human cancer, but its clinical significance and functional roles in NSCLC remain largely unclear. In the present study, JMJD1A was frequently upregulated in NSCLC compared with para-carcinoma tissues. JMJD1A knockdown significantly inhibited NSCLC cell growth, migration, and invasion in vitro and tumorigenesis in vivo. Further experiments demonstrated that JMJD1A knockdown could decrease the expression of EZH2, which has been shown to play a crucial role in the carcinogenesis of NSCLC and, in turn, increase the expression of anti-tumor microRNA let-7c. Also, let-7c directly targeted the 3′-untranslated regions of JMJD1A and EZH2. Taken together, JMJD1A could promote NSCLC tumorigenesis. JMJD1A/EZH2/let-7c constituted a feedback loop and might represent a promising therapeutic target for NSCLC.

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Acknowledgments

This work was supported by the 863 Project (No. 2012AA02A517), Medical Scientific Research Foundation of Guangdong Province (No. B2014362), and National Natural Science Foundation of China (No. 81260337).

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Authors and Affiliations

  1. Shen Zhen Children’s Hospital, Shenzhen, 510038, China

    Min Zhan, Feiqiu Wen, Zebin Chen & Hong Wei

  2. Jiangxi Provincial Cancer Hospital, Nanchang, 330029, China

    Lijuan Liu

  3. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China

    Honghao Zhou

  4. Institute of Clinical Pharmacology, Central South University, Changsha, 410008, China

    Honghao Zhou

  5. Hunan Key Laboratory of Pharmacogenetics, Changsha, 410008, China

    Honghao Zhou

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  1. Min Zhan
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  2. Feiqiu Wen
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  3. Lijuan Liu
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  5. Hong Wei
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Correspondence to Honghao Zhou.

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Zhan, M., Wen, F., Liu, L. et al. JMJD1A promotes tumorigenesis and forms a feedback loop with EZH2/let-7c in NSCLC cells. Tumor Biol. 37, 11237–11247 (2016). https://doi.org/10.1007/s13277-016-4999-9

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  • DOI: https://doi.org/10.1007/s13277-016-4999-9

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