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Retinoic Acid Receptor α Knockdown Suppresses the Tumorigenicity of Esophageal Carcinoma via Wnt/β-catenin Pathway

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Abstract

Background

Aberrant expression of retinoic acid receptor α (RARα) was correlated with diverse carcinomas such as acute promyelocytic leukemia and colorectal carcinoma. Nevertheless, the function and mechanism of RARα in esophageal carcinoma (EC) remain unclear.

Aim

To investigate the expression of RARα in EC and its effect in the tumorigenesis of EC.

Methods and Results

In immunohistochemistry study, RARα was overexpressed in human EC tissues, and its overexpression was closely related to the pathological differentiation, lymph node metastasis, and clinical stages in EC patients. Functionally, RARα knockdown suppressed the proliferation and metastasis of EC cells through downregulating the expression of PCNA, Ki67, MMP7, and MMP9, as well as enhanced drug susceptibility of EC cells to 5-fluorouracil and cisplatin. Mechanistically, RARα knockdown inhibited the activity of Wnt/β-catenin pathway through reducing the phosphorylation level of GSK3β at Ser-9 and inducing phosphorylation level at Tyr-216, which resulted in downregulation of its downstream targets such as MMP7, MMP9, and P-gP.

Conclusions

Our results demonstrated that RARα knockdown suppressed the tumorigenicity of EC via Wnt/β-catenin pathway. RARα might be a potential molecular target for EC clinical therapy.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (Grant No. 81572394); Project of Natural Science Foundation of Science and Technology Department, Fujian, China (Grant No. 2015J01545); and Special fund of Marine economic development in Xiamen (Grant No. 17GYY011HJ05).

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Author notes

  1. Xiao-Mei Mao, Hua Li, and Xiao-Yun Zhang have contributed equally to this work.

Authors and Affiliations

  1. Key Lab of the Ministry of Education for Coastal and Wetland Ecosystems, School of Life Sciences, Xiamen University, Xiangan South Road, Xiamen, 361102, Fujian, China

    Xiao-Mei Mao, Pan Zhou, Qi-Rui Fu, Qian-En Chen & Qing-Xi Chen

  2. Department of Gastroenterology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian, China

    Hua Li

  3. Department of Biobank, The First Affiliated Hospital of Xiamen University, No. 55 Zhenhai Road, Xiamen, 361003, Fujian, China

    Xiao-Yun Zhang, Jin-Xing Shen, Yu Liu & Dong-Yan Shen

Authors
  1. Xiao-Mei Mao
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  2. Hua Li
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  8. Yu Liu
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Contributions

XMM and HL wrote the manuscript and were involved in data collection. PZ and QRF were involved in the creation of the figures. XYZ, JXS, and YL analyzed the data. QXC and DYS conceived and revised the manuscript. All authors edited the manuscript and have approved its final version.

Corresponding authors

Correspondence to Qing-Xi Chen or Dong-Yan Shen.

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Conflict of interest

All authors declare that they have no competing financial interests related to this work.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institute Research Ethics Committee of the First Affiliated Hospital of Xiamen University.

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Mao, XM., Li, H., Zhang, XY. et al. Retinoic Acid Receptor α Knockdown Suppresses the Tumorigenicity of Esophageal Carcinoma via Wnt/β-catenin Pathway. Dig Dis Sci 63, 3348–3358 (2018). https://doi.org/10.1007/s10620-018-5254-6

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  • DOI: https://doi.org/10.1007/s10620-018-5254-6

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