Wang Y, Zhang YJ. Tankyrase 2 promotes lung cancer cell malignancy. World J Clin Oncol 2024; 15(6): 755-764 [PMID: 38946832 DOI: 10.5306/wjco.v15.i6.755]
Corresponding Author of This Article
Yong-Jun Zhang, MMed, Associate Chief Physician, Department of Integrated Traditional Chinese and Western Medicine, Zhejiang Cancer Hospital, No. 1 Banshan Eastern Road, Hangzhou 310022, Zhejiang Province, China. zhangyongjun770323@163.com
Research Domain of This Article
Oncology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. Jun 24, 2024; 15(6): 755-764 Published online Jun 24, 2024. doi: 10.5306/wjco.v15.i6.755
Tankyrase 2 promotes lung cancer cell malignancy
Ying Wang, Yong-Jun Zhang
Ying Wang, Department of Gynecological Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, China
Yong-Jun Zhang, Department of Integrated Traditional Chinese and Western Medicine, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, China
Author contributions: Wang Y and Zhang YJ designed the research study; Zhang YJ performed the research, analyzed the data, and wrote the manuscript; Wang Y revised the manuscript. All the authors have read and approved the final manuscript.
Supported byTraditional Chinese Medicine Foundation of Zhejiang Province, No. 2019ZA020.
Conflict-of-interest statement: The authors declare no conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset are available from the corresponding author at zhangyongjun770323@163.com.
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: Yong-Jun Zhang, MMed, Associate Chief Physician, Department of Integrated Traditional Chinese and Western Medicine, Zhejiang Cancer Hospital, No. 1 Banshan Eastern Road, Hangzhou 310022, Zhejiang Province, China. zhangyongjun770323@163.com
Received: February 25, 2024 Revised: May 9, 2024 Accepted: May 28, 2024 Published online: June 24, 2024 Processing time: 119 Days and 18 Hours
Abstract
BACKGROUND
Tankyrase 2 (TNKS2) is a potential candidate molecular target for the prognosis and treatment of non-small cell lung cancer (NSCLC), but its biological functions are unclear.
AIM
To investigate the biological functions of TNKS2 in NSCLC.
METHODS
Using a lentiviral vector, we generated H647 model cells with TNKS2 knockdown by RNA interference and A549 model cells with TNKS2 overexpression by transfection with a TNKS2 overexpressing plasmid. Increased and decreased expression levels of TNKS2 in the two cell lines were verified using real-time reverse transcriptase-polymerase chain reaction and Western blot analyses. Cell apoptosis, proliferation, and migration were determined using flow cytometry, carboxyfluorescein succinimidyl ester staining, and scratch assay, respectively. Immunofluorescence staining was conducted to examine TNKS2 and β-catenin expression levels in the two transfected cell lines and the non-transfected cells.
RESULTS
TNKS2 mRNA and protein expression was significantly higher in the highly malignant NCI-H647 cells, while it remained at a low level in the less malignant A549 cells. Lentivirus-mediated overexpression of TNKS2 in A549 cells resulted in a 3-fold increase in gene expression and a 1.7-fold increase in protein expression (P < 0.01). Conversely, shRNA interference targeting TNKS2 Led to an 8-fold decrease in gene expression and a 3-fold decrease in protein expression (P < 0.01) in NCI-H647 cells. Furthermore, the cell apoptosis rate was significantly reduced (50%) and cell migration rate was increased (35%) in the TNKS2 overexpression group than in the control group (P < 0.05). In contrast, shTNKS2 promoted apoptosis by more than one fold and reduced migration by 60% (P < 0.05). Immunofluorescence analysis revealed enhanced nuclear localization of β-catenin fluorescence signal associated with high TNKS2 expression levels. Western blot analysis investigating TNKS2/β-catenin-related proteins indicated consistent changes between TNKS2 and β-catenin expression in lung cancer cells, whereas Axin displayed an opposite trend (P < 0.05).
CONCLUSION
The obtained results revealed that TNKS2 may serve as an adverse prognostic factor and a potential therapeutic target in NSCLC.
Core Tip: This study provides a comprehensive overview of the role of tankyrase 2 (TNKS2) overexpression, which facilitates β-catenin activation and nuclear accumulation of β-catenin protein in non-small cell lung cancer (NSCLC) cells, in turn contributing to disease onset and progression. The findings obtained herein elucidate that TNKS2 is a putative molecular target candidate, which would serve as a prognostic indicator and a therapeutic agent for NSCLC patients.
