Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Dec 15, 2023; 15(12): 2185-2196
Published online Dec 15, 2023. doi: 10.4251/wjgo.v15.i12.2185
Paired-related homeobox 1 induces epithelial-mesenchymal transition in oesophageal squamous cancer
Jin-Bao Guo, Ming Du, Bin Wang, Li Zhong, Zhong-Xue Fu, Jin-Lai Wei
Jin-Bao Guo, Ming Du, Bin Wang, Department of Thoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
Li Zhong, Department of Obstetrics and Gynaecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
Zhong-Xue Fu, Jin-Lai Wei, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
Author contributions: Guo JB and Zhong L designed the research and wrote the paper; Wei JL performed the research and analyzed results; Du M, Wang B, and Fu ZX edited the manuscript and provided critical comments.
Institutional review board statement: All experimental protocols were approved by the Ethics Committee the First Affiliated Hospital of Chongqing Medical University (Approval number 2021-033).
Institutional animal care and use committee statement: All experimental protocols were approved by the Ethics Committee the First Affiliated Hospital of Chongqing Medical University (Approval number 2021-033).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at zhongli401@126.com.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Li Zhong, PhD, Academic Editor, Doctor, Researcher, Department of Obstetrics and Gynaecology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuanjiagang Street, Chongqing 400016, China. zhongli401@126.com
Received: August 15, 2023
Peer-review started: August 15, 2023
First decision: October 9, 2023
Revised: October 16, 2023
Accepted: November 9, 2023
Article in press: November 9, 2023
Published online: December 15, 2023
Processing time: 117 Days and 4.6 Hours
Abstract
BACKGROUND

It is unclear that paired-related homeobox 1 (PRRX1) induces epithelial-mesenchymal transition (EMT) in oesophageal cancer and the specific function of PRRX1 in oesophageal cancer metastasis.

AIM

To assess the significance of PRRX1 expression and investigate the mechanism of EMT in oesophageal cancer metastasis.

METHODS

Detect the expression of PRRX1 by immunohistochemistry in oesophageal tumour tissues and adjacent normal oesophageal tissues; the PRRX1 short hairpin RNA (shRNA) or blank vector lentiviral gene delivery system was transfected into cells; cell proliferation assay, soft agar colony formation assays, cell invasion and migration assays and animal studies were used to observe cells biological characteristics In vitro and in vivo; XAV939 and LiCl were used to alter the activity of Wnt/β-catenin pathway. Immunofluorescence staining and western blot analysis were used to detect protein expression of EMT markers and Wnt/β-catenin pathway.

RESULTS

PRRX1 is expressed at high levels in oesophageal cancer specimens and is closely related to tumour metastasis in patients with oesophageal cancer. Regulation of PRRX1 expression might exert obvious effects on cell proliferation, especially the migration and invasion of oesophageal cancer cells. Moreover, silencing PRRX1 expression using a shRNA produced the opposite effects. In addition, when PRRX1 was overexpressed, inhibition of the Wnt/β-catenin pathway with XAV939 negated the effect of PRRX1 on EMT, whereas when PRRX1 was downregulated, activation of the Wnt/β-catenin pathway with LiCl impaired the effect on EMT.

CONCLUSION

PRRX1 is upregulated in oesophageal cancer is closely correlated with cancer metastasis. Additionally, PRRX1 induces EMT in oesophageal cancer metastasis through activation of Wnt/β-catenin signalling.

Keywords: Paired-related homeobox 1, Oesophageal squamous cancer, Epithelial-mesenchymal transition, Cancer metastasis

Core Tip: This study aims to assess the significance of paired-related homeobox 1 (PRRX1) expression and investigate the mechanism of epithelial-mesenchymal transition (EMT) in oesophageal cancer metastasis. PRRX1 is expressed at high levels in oesophageal cancer specimens and is closely related to tumour metastasis in patients with oesophageal cancer. Regulation of PRRX1 expression might exert obvious effects on cell proliferation, especially the migration and invasion of oesophageal cancer cells. Moreover, silencing PRRX1 expression using a short hairpin RNA produced the opposite effects. In addition, when PRRX1 was overexpressed, inhibition of the Wnt/β-catenin pathway with XAV939 negated the effect of PRRX1 on EMT, whereas when PRRX1 was downregulated, activation of the Wnt/β-catenin pathway with LiCl impaired the effect on EMT. These observations indicate that PRRX1 is upregulated in oesophageal cancer is closely correlated with cancer metastasis. Additionally, PRRX1 induces EMT in oesophageal cancer metastasis through activation of Wnt/β-catenin signalling.