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α7-Nicotinic Acetylcholine Receptor Promotes Cholangiocarcinoma Progression and Epithelial–Mesenchymal Transition Process

  • Shuhai Chen
  • Xiaoliang Kang
  • Guangwei Liu
  • Bingyuan Zhang
  • Xiao Hu
  • Yujie FengEmail author
Original Article

Abstract

Background

Cholangiocarcinoma is one of the most deadly malignant tumors characterized by a tendency of local invasiveness and metastasis at the early phase, high recurrence rate, and difficulty in treatment. Alpha7-nicotinic acetylcholine receptor (α7-nAChR) is highly expressed in a variety of tumors, including cholangiocarcinoma, and may promote tumor progression, but the mechanisms are largely unknown.

Aims

Our study is the first to expound upon the role that α7-nAChR plays in cholangiocarcinoma.

Methods

We assessed 50 human cholangiocarcinoma tissue samples and 20 normal biliary samples using immunohistochemical staining to find the correlation between α7-nAChR expression and clinicopathological characteristics. We used human cholangiocarcinoma cell lines QBC939 and RBE and α7-nAChR gene knockdown RBE cell lines generated by shRNA lentivirus transfection to investigate the biological functions of α7-nAChR in proliferation, apoptosis, migration, and invasiveness in vitro. Further, western blotting was used to detect apoptosis and epithelial–mesenchymal transition (EMT)-related signaling proteins. Cholangiocarcinoma xenografts in nude mice were used for tumorigenicity assays in vivo.

Results

The expression of α7-nAChR was high in cholangiocarcinoma tissues and was closely related to a shorter survival time in patients. α7-nAChR knockdown decreased cell proliferation ability, increased early apoptosis, and weakened cell migration and invasion. Apoptosis-related proteins and components of the EMT process were altered after α7-nAChR knockdown. Moreover, nude mice xenograft experiments confirmed that α7-nAChR could promote cholangiocarcinoma in vitro.

Conclusions

Overexpression of α7-nAChR induces cholangiocarcinoma progression by blocking apoptosis and promoting the EMT process. As an effective molecular biomarker and prognostic factor, α7-nAChR is a promising therapeutic target in cholangiocarcinoma.

Keywords

α-7 Nicotinic acetylcholine receptor Cholangiocarcinoma Apoptosis Epithelial–mesenchymal transition Anticancer 

Notes

Acknowledgments

This work was supported by a Grant from the National Natural Science Foundation of China (No. 81272362).

Author’s contribution

YJF and BYZ designed and supervised the experiments. SHC and XLK performed the experiments. SHC and HX collected the data. SHC and GWL analyzed the data. BYZ provided the human samples. SHC and YJF wrote the manuscript. All authors read and approved the final manuscript.

Funding

This work was supported by a Grant from the National Natural Science Foundation of China (No. 81272362).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval and consent to participate

All procedures in this study that involved human participants were performed in accordance with the 1964 Helsinki declaration and its later amendments. The protocol was approved by the Ethics Committee of The Affiliated Hospital of Qingdao University. Informed consent was obtained from all individual participants included in the study. Furthermore, the care and use of laboratory animals was in accordance with the principles and standards set forth in the Principles for Use of Animals (National Guide for Grants and Contracts).

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Shuhai Chen
    • 1
  • Xiaoliang Kang
    • 1
  • Guangwei Liu
    • 2
  • Bingyuan Zhang
    • 1
  • Xiao Hu
    • 1
  • Yujie Feng
    • 1
    Email author
  1. 1.Department of Hepatobiliary and Pancreatic SurgeryThe Affiliated Hospital of Qingdao UniversityQingdaoChina
  2. 2.Department of OutpatientThe Affiliated Hospital of Qingdao UniversityQingdaoChina

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