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
Processing time: 136 Days and 5.5 Hours
Abstract
BACKGROUND

Bioinformatics analysis showed that the expression of the poly(A)-specific ribonuclease (PARN) gene in gastric cancer, head and neck squamous cell carcinoma, melanoma, cervical cancer and lung squamous cell carcinoma tissues was significantly higher than that in normal tissues and was associated with high stage and poor prognosis. The expression of the PARN gene in esophageal cancer (EC) tissue is also significantly higher than that in normal tissues, but the effect of PARN on the proliferation, migration and invasion of EC cells remains unclear.

AIM

To investigate the relationship between PARN and the proliferation, migration and invasion of EC cells.

METHODS

The EC tissues of 91 patients after EC surgery and 63 paired precancerous healthy tissues were collected. PARN mRNA levels were measured using a tissue microarray, and the PARN expression level was evaluated using immunohistochemistry to analyze the relationship between PARN expression and clinicopathologic features as well as the survival and prognosis of patients. In addition, the effects of PARN gene knockout on tumor cell proliferation, invasion and migration were studied by using shRNA during the in vitro culture of EC cell lines Eca-109 and TE-1, and the effects of the PARN gene on tumor growth in vivo were verified by a xenotransplantation nude mice model.

RESULTS

The expression of PARN in EC tissues was higher than that in adjacent normal tissues, and the level of PARN expression was significantly positively correlated with lymphatic metastasis. Patients with high PARN levels had poor overall survival. BIM, IGFBP-5 and p21 levels were significantly increased in the PARN knockout group, while the expression levels of the antiapoptotic proteins Survivin and sTNF-R1 were significantly decreased in the apoptotic antibody array data. In addition, the expression levels of Akt, p-Akt, PIK3CA and CCND1 in the downstream signaling pathway regulating EC progression were significantly decreased. The culture of EC cell lines confirmed that the apoptosis rate of EC cells was significantly increased, the growth and proliferation of tumor cells were significantly inhibited, and the invasion and migration ability of tumor cells were significantly decreased after PARN gene knockout. In vivo experiments of BALB/c nude mice transfected with Eca-109 cells expressing control shRNA (sh-NC) and PARN shRNA (sh-PARN) showed that the tumor volume and weight of nude mice treated with sh-PARN were significantly decreased compared with those of nude mice treated with sh-NC, indicating that PARN knockdown significantly inhibited tumor growth in vivo.

CONCLUSION

PARN has antiapoptotic effects on EC cells and promotes their proliferation, invasion and migration, which is associated with the development of EC and poor patient prognosis. PARN may become a potential target for the diagnosis, prognosis prediction and treatment of EC.

Keywords: Poly(A)-specific ribonuclease; Esophageal cancer; Apoptotic; Phosphatidylinositol 3-kinase/protein kinase B

Core Tip: Bioinformatics analysis showed that the expression of the poly(A)-specific ribonuclease (PARN) gene in gastric cancer, head and neck squamous cell carcinoma, melanoma, cervical cancer and lung squamous cell carcinoma tissues was significantly higher than that in normal tissues and was associated with high stage and poor prognosis. The expression of the PARN gene in esophageal cancer (EC) tissue is also significantly higher than that in normal tissues, but the effect of PARN on the proliferation, migration and invasion of EC cells remains unclear. This study investigated the relationship between PARN and the proliferation, migration and invasion of EC cells.