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Hypoxia-induced LncRNA PCGEM1 promotes invasion and metastasis of gastric cancer through regulating SNAI1

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Abstract

Purpose

Hypoxia is an indispensable factor in the progression of metastasis. Hypoxia inducible factor-1α (HIF-1α), the core element in generating the hypoxia response, induces invasion and metastasis by promoting epithelial–mesenchymal transition (EMT). This study explored the underlying mechanism of hypoxia associated with the invasion and metastasis of gastric cancer (GC).

Methods

Six methods were employed to assess the function of the long noncoding RNA (lncRNA) prostate cancer gene expression marker 1 (PCGEM1) including gene silencing, RT-PCR, the separation of nuclear and cytoplasmic fractions, scrape motility assay, transwell migration assay, and Western-blot.

Results

LncRNA PCGEM1 was overexpressed in GC cells and tissues, and was induced by hypoxia in GC cells. Additional experiments confirmed that the knockdown of PCGEM1 significantly repressed the invasion and metastasis of GC cells. SNAI1, a key transcription factor of EMT, was regulated by PCGEM1. Overexpression of SNAI1 rescued the inhibition of PCGEM1-knockdown during the invasion and metastasis of GC cells. In addition, PCGEM1 and SNAI1 jointly affected the biomarkers of EMT.

Conclusion

Our findings indicated that PCGEM1 is a hypoxia-responsive lncRNA, and contributes to the invasion and metastasis of GC. The potential mechanism is attributed to the regulation of EMT by PCGEM1 and its influence on the expression of SNAI1.

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Funding

Liaoning S&T Project (20180550971). Liaoning provincial special Fund for central guiding local science and technology development plan (2018416017)

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Authors and Affiliations

  1. Gastric Cancer Department, Liaoning Province Cancer Hospital and Institute (Cancer Hospital of China Medical University), No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning, China

    J. Zhang, Z. C. Zheng, S. Guo, Y. Wang, D. Yang, X. Y. Meng, X. Xu & Y. Zhao

  2. Pancreatic and Thyroid Surgery Department, Sheng Jing Hospital of China Medical University, 36 Sanhao St, Heping District, Shenyang, 110003, Liaoning, China

    H. Y. Jin

  3. Emergency Department, Sheng Jing Hospital of China Medical University, 36 Sanhao St, Heping District, Shenyang, 110003, Liaoning, China

    Y. Wu

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  1. J. Zhang
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  4. Z. C. Zheng
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Contributions

ZJ performed the majority of experiments and analyzed the data and drafted the manuscript; ZZC, ZY designed the research; WY, YD, MXY conducted the molecular biology assays and assisted in writing the manuscript; GS, WY collected and analyzed the data; ZY provided critical revision of the manuscript for important intellectual content. JHY provided critical revision of the manuscript for important intellectual content.

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Correspondence to Y. Zhao.

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Zhang, J., Jin, H.Y., Wu, Y. et al. Hypoxia-induced LncRNA PCGEM1 promotes invasion and metastasis of gastric cancer through regulating SNAI1. Clin Transl Oncol 21, 1142–1151 (2019). https://doi.org/10.1007/s12094-019-02035-9

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  • DOI: https://doi.org/10.1007/s12094-019-02035-9

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