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Upregulation of long noncoding RNA SPRY4-IT1 promotes metastasis of esophageal squamous cell carcinoma via induction of epithelial–mesenchymal transition

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Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the prevalent and deadly cancers worldwide, especially in Eastern Asia. Recent studies show that long noncoding RNAs (lncRNAs) have critical roles in diverse biological processes, including tumorigenesis. In the present study, we find that the expression of lncRNA SPRY4-IT1 is significantly upregulated in ESCC cell lines as compared with human esophageal epithelial cell line HEEC. Overexpression of SPRY4-IT1 can increase in vitro motility of ESCC cells via induction of epithelial–mesenchymal transition (EMT), which is characterized by increasing the expression of vimentin (Vim) and fibronectin (FN) with a concomitant decrease of E-cadherin (E-Cad) and ZO-1, while silencing of SPRY4-IT1 significantly inhibits the in vitro motility of ESCC cells. Further, the knockdown of SPRY4-IT1 also significantly attenuates TFG-β-induced EMT of ESCC cells. Further, lncRNA SPRY4-IT1 can directly increase the transcription, expression, and nuclear localization of Snail, one key transcription factor during the EMT processes of cancer cells, while siRNA-mediated specific knockdown of Snail can significantly attenuate SPRY4-IT1-induced EMT of ESCC cells. Our results suggest that lncRNA SPRY4-IT1 might be considered as a novel oncogene involved in ESCC progression.

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Acknowledgments

This research was supported by the Henan Province High Education Territory Science and Technology Innovation Team (13IRTSTHN011).

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    Authors and Affiliations

    1. Department of Thoracic Surgery, The First Affiliated Hospital, Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, Henan, 450052, China

      Chun-Yang Zhang, Yu Qi, Xiang-Nan Li, Yang Yang, Dong-Lei Liu, Jia Zhao, Deng-Yan Zhu, Kai Wu, Xu-Dong Zhou & Song Zhao

    2. Open Key Clinical Medical Experimental Laboratory Institute of Henan Province, Zhengzhou, Henan, 450052, China

      Chun-Yang Zhang, Yu Qi, Xiang-Nan Li, Yang Yang, Dong-Lei Liu, Jia Zhao, Deng-Yan Zhu, Kai Wu, Xu-Dong Zhou & Song Zhao

    3. Diagnosis and Treatment of Lung Cancer Research Center, Zhengzhou University, Zhengzhou, Henan, 450052, China

      Chun-Yang Zhang, Yu Qi, Xiang-Nan Li, Yang Yang, Dong-Lei Liu, Jia Zhao, Deng-Yan Zhu, Kai Wu, Xu-Dong Zhou & Song Zhao

    4. Key Laboratory of Thoracic Tumors of Zhengzhou, Zhengzhou, Henan, 450052, China

      Chun-Yang Zhang, Yu Qi, Xiang-Nan Li, Yang Yang, Dong-Lei Liu, Jia Zhao, Deng-Yan Zhu, Kai Wu, Xu-Dong Zhou & Song Zhao

    5. Department of Anesthesiology, Orthopaedic Hospital of Zhengzhou, Zhengzhou, Henan, 450052, China

      Ren-Ke Li

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    1. Chun-Yang Zhang
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    Correspondence to Song Zhao.

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    Chun-Yang Zhang and Ren-Ke Li contributed equally to this work.

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    Zhang, CY., Li, RK., Qi, Y. et al. Upregulation of long noncoding RNA SPRY4-IT1 promotes metastasis of esophageal squamous cell carcinoma via induction of epithelial–mesenchymal transition. Cell Biol Toxicol 32, 391–401 (2016). https://doi.org/10.1007/s10565-016-9341-1

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