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ZFPM2-AS1, a novel lncRNA, attenuates the p53 pathway and promotes gastric carcinogenesis by stabilizing MIF

Oncogene volume 37, pages 5982–5996 (2018)Cite this article

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A Correction to this article was published on 14 August 2018

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Abstract

Long non-coding RNAs (lncRNAs) are implicated to be involved in the pathogenesis of many cancers. Herein we report on our discovery of a novel lncRNA, ZFPM2 antisense RNA 1 (ZFPM2-AS1), and its critical role in gastric carcinogenesis. ZFPM2-AS1 expression in gastric cancer specimens was analyzed using Gene Expression Omnibus data set and validated in 73 paired gastric tumor and normal adjacent gastric tissue specimens using qRT-PCR. The effect of ZFPM2-AS1 expression on proliferation and apoptosis in gastric cancer cells was assessed by altering its expression in vitro and in vivo. Mechanistic investigation was carried out using cell and molecular biological approaches. ZFPM2-AS1 expression was higher in gastric tumors than in normal gastric tissue. Also, increased ZFPM2-AS1 expression in gastric cancer specimens was associated with tumor size, depth of tumor invasion, differentiation grade, and TNM stage. High ZFPM2-AS1 expression predicted markedly reduced overall and disease-free survival in gastric cancer patients. Functional experiments demonstrated that ZFPM2-AS1 expression promoted proliferation and suppressed apoptosis of gastric cancer cells in vitro and promoted tumor growth in vivo. This effect is associated with attenuated nuclear translocation of p53. Mechanistic experiments demonstrated that tumor-activated ZFPM2-AS1 could bind to and protect the degradation of macrophage migration inhibitory factor (MIF), a potent destabilizer of p53. Knockdown of MIF expression diminished ZFPM2-AS1’s impact on p53 expression in gastric cancer cells. Our findings demonstrated that ZFPM2-AS1 regulates gastric cancer progression and revealed a novel ZFPM2-AS1/MIF/p53 signaling axis, shedding light on the molecular mechanisms underlying the tumorigenicity of certain malignant gastric cells.

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  • 14 August 2018

    Since the online publication of the above article, the authors have noted errors in the affiliations. The authors apologise for any inconvenience caused by this error. The html and online pdf versions have now been rectified and carry the corrected paper.

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Acknowledgements

We would like to thank Don Norwood for editing the manuscript.

Funding

This work was supported by grants R01CA172233, R01CA195651, and R01CA198090 from the National Cancer Institute, National Institutes of Health (to K.X.) and grant 81772640 from the National Natural Science Foundation of China (to X.K.).

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  1. These authors contributed equally: Fanyang Kong, Xuan Deng, Xiangyu Kong.

Affiliations

  1. Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China

    Fanyang Kong, Xiangyu Kong, Yiqi Du, Lei Li, Huiyun Zhu, Yuxin Wang & Zhaoshen Li

  2. Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Fanyang Kong, Xiangyu Kong, Dacheng Xie, Shivani Guha & Keping Xie

  3. Department of Laboratory Medicine, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China

    Xuan Deng & Ming Guan

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Kong, F., Deng, X., Kong, X. et al. ZFPM2-AS1, a novel lncRNA, attenuates the p53 pathway and promotes gastric carcinogenesis by stabilizing MIF. Oncogene 37, 5982–5996 (2018). https://doi.org/10.1038/s41388-018-0387-9

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