Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Feb 15, 2024; 16(2): 458-474
Published online Feb 15, 2024. doi: 10.4251/wjgo.v16.i2.458
Immune-related long noncoding RNA zinc finger protein 710-AS1-201 promotes the metastasis and invasion of gastric cancer cells
Wei Ding, Wei-Wei Chen, Yi-Qin Wang, Xue-Zhong Xu, Yi-Bo Wang, Yong-Min Yan, Yu-Lin Tan
Wei Ding, Wei-Wei Chen, Yi-Qin Wang, Xue-Zhong Xu, Yi-Bo Wang, Yu-Lin Tan, Department of General Surgery, Wujin Hospital Affiliated with Jiangsu University, Changzhou 213003, Jiangsu Province, China
Wei Ding, Yong-Min Yan, Changzhou Medical Center, Nanjing Medical University, Changzhou 213017, Jiangsu Province, China
Wei Ding, Yu-Lin Tan, Department of General Surgery, The Wujin Clinical College of Xuzhou Medical University, Changzhou 213003, Jiangsu Province, China
Author contributions: Ding W contributed to conceptualization; Chen WW and Wang YB contributed to methodology; Wang YQ contributed to validation; Wang YB contributed to formal analysis; Xu XZ contributed to resources; Ding W contributed to writing original draft preparation; Ding W and Tan YL contributed to writing-review and editing; Yan YM contributed to supervision; Tan YL contributed to project administration; Ding W and Tan YL contributed to funding acquisition; all authors contributed to the study and approved the submitted version of the manuscript.
Supported by Changzhou Sci and Tech Program, No. CJ20220008; Young Talent Development Plan of Changzhou Health Commission, No. CZQM2020118; Changzhou High-Level Medical Talents Training Project, No. 2022CZBJ105; Cultivation Project of Changzhou Medical Center, Nanjing Medical University, No. CMCB202211; and Development Foundation of Affiliated Hospital of Xuzhou Medical University, No. XYFC202304, and No. XYFM202307.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board at Wujin Hospital affiliated with Jiangsu University approved this study.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Wujin Hospital affiliated with Jiangsu University.
Conflict-of-interest statement: All other authors have nothing to disclose.
Data sharing statement: No additional data are available.
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: Yu-Lin Tan, MMed, Chief Physician, Department of General Surgery, Wujin Hospital Affiliated with Jiangsu University, No. 2 Yongning Road, Changzhou 213003, Jiangsu Province, China. tanyldoctor@163.com
Received: September 4, 2023
Peer-review started: September 4, 2023
First decision: November 22, 2023
Revised: December 2, 2023
Accepted: December 20, 2023
Article in press: December 20, 2023
Published online: February 15, 2024
Processing time: 150 Days and 21.1 Hours
Abstract
BACKGROUND

Gastric cancer (GC) is a prevalent malignant tumor of the gastrointestinal system. ZNF710 is a transcription factor (TF), and zinc finger protein 710 (ZNF710)-AS1-201 is an immune-related long noncoding RNA (lncRNA) that is upregulated in GC cells.

AIM

To assess the correlation between ZNF710-AS1-201 and immune microenvironment features and to investigate the roles of ZNF710-AS1-201 in the invasion and metastasis processes of GC cells.

METHODS

We obtained data from The Cancer Genome Atlas and Wujin Hospital. We assessed cell growth, migration, invasion, and programmed cell death using cell counting kit-8, EdU, scratch, Transwell, and flow cytometry assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to identify the potential downstream targets of ZNF710-AS1-201.

RESULTS

In GC tissues with low ZNF710-AS1-201 expression, immunoassays detected significant infiltration of various antitumor immune cells, such as memory CD8 T cells and activated CD4 T cells. In the low-expression group, the half-maximal inhibitory concentrations (IC50s) of 5-fluorouracil, cisplatin, gemcitabine, and trametinib were lower, whereas the IC50s of dasatinib and vorinostat were higher. The malignant degree of GC was higher and the stage was later in the high-expression group. Additionally, patients with high expression of ZNF710-AS1-201 had lower overall survival and disease-free survival rates. In vitro, the overexpression of ZNF710-AS1-201 greatly enhanced growth, metastasis, and infiltration while suppressing cell death in HGC-27 cells. In contrast, the reduced expression of ZNF710-AS1-201 greatly hindered cell growth, enhanced apoptosis, and suppressed the metastasis and invasion of MKN-45 cells. The expression changes in ZNF710 were significant, but the corresponding changes in isocitrate dehydrogenase-2, Semaphorin 4B, ARHGAP10, RGMB, hsa-miR-93-5p, and ZNF710-AS1-202 were not consistent or statistically significant after overexpression or knockdown of ZNF710-AS1-201, as determined by qRT-PCR.

CONCLUSION

Immune-related lncRNA ZNF710-AS1-201 facilitates the metastasis and invasion of GC cells. It appears that ZNF710-AS1-201 and ZNF710 have potential as effective targets for therapeutic intervention in GC. Nevertheless, it is still necessary to determine the specific targets of the ZNF710 TF.

Keywords: Gastric cancer; ZNF710-AS1-201; Proliferation; Metastasis; Invasion; Apoptosis

Core Tip: In the field of oncology, there is significant interest in long noncoding RNAs (lncRNAs). They have a significant impact on the immune microenvironments of tumors and immunotherapy. In addition, lncRNAs regulate many crucial mechanisms of cancer immunity, including the presentation of antigens and the exhaustion of T cells. According to our prior investigation, the immune-associated lncRNA zinc finger protein 710 (ZNF710)-AS1-201 has the potential to function as an indicator of GC patient prognosis (recurrence, metastasis and survival). The primary focus of this study was to assess the correlation between ZNF710-AS1-201 and the immune microenvironment and to investigate the roles of ZNF710-AS1-201 in the cellular growth and metastasis processes within GC cells.