Liu N, Liu J, Wang YL, Zhu L, Zhu CW. Knockdown of 5-methylcytosine RNA methyltransferase NOP2/sun RNA methyltransferase 5 in hepatocellular carcinoma cells affects their biological functions. World J Gastrointest Surg 2026; 18(1): 112243 [DOI: 10.4240/wjgs.v18.i1.112243]
Corresponding Author of This Article
Chuan-Wu Zhu, Chief Physician, Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital, Suzhou Medical College of Soochow University, No. 10 Guangqian Road, Xiangcheng District, Suzhou 215131, Jiangsu Province, China. zhuchw@126.com
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Infectious Diseases
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Jan 27, 2026 (publication date) through Jan 28, 2026
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World Journal of Gastrointestinal Surgery
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1948-9366
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Liu N, Liu J, Wang YL, Zhu L, Zhu CW. Knockdown of 5-methylcytosine RNA methyltransferase NOP2/sun RNA methyltransferase 5 in hepatocellular carcinoma cells affects their biological functions. World J Gastrointest Surg 2026; 18(1): 112243 [DOI: 10.4240/wjgs.v18.i1.112243]
World J Gastrointest Surg. Jan 27, 2026; 18(1): 112243 Published online Jan 27, 2026. doi: 10.4240/wjgs.v18.i1.112243
Knockdown of 5-methylcytosine RNA methyltransferase NOP2/sun RNA methyltransferase 5 in hepatocellular carcinoma cells affects their biological functions
Na Liu, Jin Liu, Yin-Ling Wang, Li Zhu, Chuan-Wu Zhu
Na Liu, Chuan-Wu Zhu, Department of Infectious Diseases, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China
Na Liu, Department of Infectious Diseases and Liver Diseases, The Second Hospital of Nanjing, Nanjing 210003, Jiangsu Province, China
Jin Liu, Yin-Ling Wang, Li Zhu, Chuan-Wu Zhu, Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital, Suzhou Medical College of Soochow University, Suzhou 215131, Jiangsu Province, China
Jin Liu, Chuan-Wu Zhu, Department of Hepatology, The Fifth People's Hospital of Suzhou, Suzhou 215131, Jiangsu Province, China
Author contributions: Liu N drafted the initial manuscript, reviewed and refined the final version of the manuscript; Liu N, Liu J and Wang YL handled data collection; Liu N and Zhu L carried out the data analysis; Liu N and Zhu CW conducted the experiments; all authors approved the final version of the article.
Supported by National Natural Science Foundation of China, No. 82172252; and Suzhou Major Disease Multicenter Clinical Research Project, No. DZXYJ202310.
Conflict-of-interest statement: There is no conflict of interest.
Data sharing statement: No additional data are available.
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: Chuan-Wu Zhu, Chief Physician, Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital, Suzhou Medical College of Soochow University, No. 10 Guangqian Road, Xiangcheng District, Suzhou 215131, Jiangsu Province, China. zhuchw@126.com
Received: September 2, 2025 Revised: October 16, 2025 Accepted: November 27, 2025 Published online: January 27, 2026 Processing time: 141 Days and 1.2 Hours
Abstract
BACKGROUND
Hepatocellular carcinoma (HCC) is among the most prevalent cancers worldwide. Recent studies have indicated that 5-methylcytosine (m5c) RNA modifications play crucial roles in various biological processes through interactions with specific regulatory factors, including their involvement in the malignant progression of multiple tumors.
AIM
To examine the impact of NOP2/sun RNA methyltransferase 5 (NSUN5), an m5c methyltransferase, on the functional behavior of HCC cells.
METHODS
NSUN5 expression in HCC and normal liver tissues was analyzed using the Gene Expression Profiling Interactive Analysis bioinformatics tool. Human normal hepatocytes (LO2) and HCC cells were examined. The m5c levels in cellular extracts and culture supernatants were quantified using enzyme-linked immunosorbent assay, while NSUN5 levels were quantified using quantitative reverse transcription polymerase chain reaction (for mRNA levels) and Western blotting (for protein levels). Changes in NSUN5 expression following silencing of NSUN5 using transfection with short hairpin RNA were determined. Functional assays were used to evaluate HCC cell growth (Cell Counting Kit-8 and Colony Formation Assays), migration and invasion (Transwell and Wound-Healing Assays), and cell cycle and apoptosis (flow cytometry).
RESULTS
NSUN5 mRNA was significantly upregulated in HCC compared with normal liver tissues, with expression levels varying across different HCC stages (P < 0.05). HCC cells – HepG2, HEP3B, Huh-7, SMMC7721, and SK-HEP-1 – showed significantly higher NSUN5 mRNA expression levels than the normal human hepatocyte line LO2 (P < 0.05). Following short hairpin RNA-mediated NSUN5 silencing, HepG2 and SMMC7721 cells exhibited reduced proliferation and growth, decreased migration and invasion, and enhanced apoptotic levels (P < 0.05); however, they showed no significant changes in cell cycles (P > 0.05).
CONCLUSION
Both HCC tissues and cell models consistently demonstrated elevated NSNU5 mRNA and protein expression. Genetic inhibition of the m5c methyltransferase NSUN5 suppresses HCC cell growth, reduces invasiveness and migration, and induces apoptosis.
Core Tip: Epigenetic modifications are dynamic, reversible, and heritable chemical changes to biomolecules that occur without altering the sequence of nuclear DNA. Among these, the RNA modification 5-methylcytosine has garnered increasing attention. However, the roles of RNA modification 5-methylcytosine modifications and their modifying enzymes in gene regulation and chromatin organization remain largely unclear. While previous studies have reported the involvement of NOP2/sun RNA methyltransferase 5 in human cancers, its comprehensive role in hepatocellular carcinoma remains unexplored. Therefore, this study evaluates the effects of NOP2/sun RNA methyltransferase 5 on hepatocellular carcinoma cell growth, migration, and invasion at the cellular level.
