Randomized Controlled Trial
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2023; 29(31): 4783-4796
Published online Aug 21, 2023. doi: 10.3748/wjg.v29.i31.4783
Poly(A)-specific ribonuclease protein promotes the proliferation, invasion and migration of esophageal cancer cells
Fu-Wei Zhang, Xiao-Wei Xie, Meng-Hua Chen, Jian Tong, Qun-Qing Chen, Jing Feng, Feng-Ti Chen, Wen-Qi Liu
Fu-Wei Zhang, Jian Tong, Qun-Qing Chen, Jing Feng, Department of Thoracic Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
Xiao-Wei Xie, Meng-Hua Chen, Feng-Ti Chen, Wen-Qi Liu, Department of Radiation Oncology, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
Author contributions: Zhang FW and Liu WQ contributed to the conceptualization of this manuscript; Tong J, Chen QQ, and Feng J collected and curated the data and contributed to the supervision of this study; Xie XW contributed to the experiments; Tong J contributed to the data analysis; Zhang FW wrote the original draft; Liu WQ contributed to the writing, review and editing of this article; and all authors reviewed, discussed, and agreed with manuscript.
Institutional review board statement: The study was reviewed and approved by the Second Affiliated Hospital of Guangxi Medical University Ethics Committee.
Clinical trial registration statement: Our study was not a prospective, randomized, controlled clinical trial and did not give a population one or more pre-defined interventions. Our study was a retrospective study of postoperative tissue samples from patients who had completed treatment. Cell experiments and animal experiments were conducted according to the results of clinical specimens. Therefore, our study should not apply the registration policy and should not require registration for clinical studies.
Informed consent statement: Written patient consent was obtained from all patients.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
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: Wen-Qi Liu, PhD, Chief Doctor, Doctor, Department of Radiation Oncology, The Second Affiliated Hospital of Guangxi Medical University, No. 166 East University Road, Nanning 530000, Guangxi Zhuang Autonomous Region, China. liuwenqigx@163.com
Received: April 4, 2023
Peer-review started: April 4, 2023
First decision: April 12, 2023
Revised: April 29, 2023
Accepted: July 27, 2023
Article in press: July 27, 2023
Published online: August 21, 2023
ARTICLE HIGHLIGHTS
Research background

Esophageal cancer (EC) is a common malignant cancer type and the sixth leading cause of cancer-related mortality worldwide. The main treatment options for esophageal squamous cell carcinoma (ESCC) include surgery, radiotherapy, and chemotherapy. Due to its high invasiveness and high recurrence and metastasis rates, the prognosis of ESCC patients remains poor despite the use of multidisciplinary treatment. The 5-year overall survival rate of ESCC patients is only 30%-40%. However, the prognosis of patients with advanced or metastatic EC is even worse, with a 5-year overall survival rate of less than 15%.

Research motivation

Poly(A)-specific ribonuclease (PARN) is a multifunctional enzyme that plays a crucial role in the occurrence and development of a variety of cancer types. The aim of this study was to explore the relationship between PARN and the proliferation, metastasis and invasion of EC cells to evaluate whether PARN could be a potential biomarker and drug target for the treatment of EC.

Research objectives

The objects of this study are as follows: (1) EC tissues and paired adjacent normal tissues were obtained from 91 patients with EC after surgery; (2) EC lines Eca-109 and TE-1; and (3) Nude mice.

Research methods

The expression of PARN mRNA was measured using a tissue microarray, and the expression of PARN was also detected using immunohistochemistry. The relationship between PARN expression and clinicopathological features and the survival prognosis of patients was analyzed. The effect of PARN on the proliferation, invasion and migration of Eca-109 and TE-1 EC cells was investigated in vitro by knocking down PARN using shRNA. The effect of PARN on tumor growth in vivo was verified by a nude mouse xenograft model.

Research results

Our study found that PARN expression in EC tissues is clearly higher than that in adjacent healthy tissues and is significantly correlated with lymph node metastasis and poor survival. It was confirmed that PARN can promote the growth and proliferation of EC cells. Compared with the control shRNA group, the PARN shRNA group exhibited a significantly increased percentage of cells in the G2/M phase, suggesting that PARN affects the proliferation of carcinoma cells by regulating their cell cycle. Knockdown of the PARN gene promoted apoptosis by regulating apoptotic proteins. Wound healing tests and transwell invasion tests confirmed the promoting effect of PARN on the migration and invasion of EC cells. In the BALB/c nude mouse xenograft model, the apoptosis ratio of Eca-109 and TE-1 cells was significantly increased after PARN knockout, and the cell proliferation rate was significantly decreased, as well as the percentage of cells in G2/M phase arrest.

Research conclusions

Our study preliminarily concluded that PARN may inhibit EC cell apoptosis and cell cycle arrest through the PI3K/Akt pathway, thus promoting tumor cell proliferation, invasion and migration and further accelerating the progression of EC.

Research perspectives

PARN can be used as a prognostic marker and therapeutic target for the diagnosis and treatment of EC.