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Digestive Diseases and Sciences

, Volume 63, Issue 12, pp 3348–3358 | Cite as

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

  • Xiao-Mei Mao
  • Hua Li
  • Xiao-Yun Zhang
  • Pan Zhou
  • Qi-Rui Fu
  • Qian-En Chen
  • Jin-Xing Shen
  • Yu Liu
  • Qing-Xi ChenEmail author
  • Dong-Yan ShenEmail author
Original Article

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.

Keywords

Retinoic acid receptor α Esophageal carcinoma Proliferation Metastasis Drug susceptibility Wnt/β-catenin pathway 

Notes

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).

Author’s contribution

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.

Compliance with ethical standards

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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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Xiao-Mei Mao
    • 1
  • Hua Li
    • 2
  • Xiao-Yun Zhang
    • 3
  • Pan Zhou
    • 1
  • Qi-Rui Fu
    • 1
  • Qian-En Chen
    • 1
  • Jin-Xing Shen
    • 3
  • Yu Liu
    • 3
  • Qing-Xi Chen
    • 1
    Email author
  • Dong-Yan Shen
    • 3
    Email author
  1. 1.Key Lab of the Ministry of Education for Coastal and Wetland Ecosystems, School of Life SciencesXiamen UniversityXiamenChina
  2. 2.Department of GastroenterologyThe First Affiliated Hospital of Xiamen UniversityXiamenChina
  3. 3.Department of BiobankThe First Affiliated Hospital of Xiamen UniversityXiamenChina

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