NSUN5 accelerates the progression of liver hepatocellular carcinoma by m5C-EFNA3-mediated glycolysis

Abstract Background Aerobic glycolysis is a hallmark of cancers including liver hepatocellular carcinoma (LIHC). RNA m5C methylation is involved in LIHC progression. However, the effect of a m5C writer, NSUN5, on glycolysis in LIHC remains not known. The present study aimed to investigate the effect...

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Main Authors: Yehong Han, Xueqin Deng, Haixia Chen, Jie Chen, Wei Xu, Lanqin Liu
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Cancer
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Online Access:https://doi.org/10.1186/s12885-025-14714-8
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author Yehong Han
Xueqin Deng
Haixia Chen
Jie Chen
Wei Xu
Lanqin Liu
author_facet Yehong Han
Xueqin Deng
Haixia Chen
Jie Chen
Wei Xu
Lanqin Liu
author_sort Yehong Han
collection DOAJ
description Abstract Background Aerobic glycolysis is a hallmark of cancers including liver hepatocellular carcinoma (LIHC). RNA m5C methylation is involved in LIHC progression. However, the effect of a m5C writer, NSUN5, on glycolysis in LIHC remains not known. The present study aimed to investigate the effect of NSUN5 on glycolysis in LIHC and the molecular mechanism. Methods NSUN5 and EFNA3 expression data were acquired from The Cancer Genome Atlas database. Cell viability and glycolysis were evaluated. Tumor growth was evaluated using the xenograft tumor model. The effect of NSUN5 on EFNA3 m5C methylation was evaluated using methylated RNA immunoprecipitation and dual-luciferase reporter assay. Results We found that NSUN5 and EFNA3 expression was increased in LIHC and related to poor survival. Knocking down NSUN5 inhibited LIHC cell viability and glycolysis in vitro, and inhibited tumor growth and glycolysis in vivo. Moreover, the expression of NSUN5 was positively correlated with that of EFNA3. NSUN5 stabilized EFNA3 by promoting m5C modification of EFNA3. Additionally, overexpression of EFNA3 reversed the inhibition of cell viability and glycolysis induced by NSUN5 silence. Conclusion Silencing of NSUN5 decelerates LIHC progression by inhibiting glycolysis mediated by EFNA3 with m5C modification, highlighting the potential of NSUN5 as a therapeutic target for LIHC.
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institution Kabale University
issn 1471-2407
language English
publishDate 2025-07-01
publisher BMC
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series BMC Cancer
spelling doaj-art-e5de5f2dc30c4cf7bffa626ae7eb81b52025-08-20T03:43:22ZengBMCBMC Cancer1471-24072025-07-0125111110.1186/s12885-025-14714-8NSUN5 accelerates the progression of liver hepatocellular carcinoma by m5C-EFNA3-mediated glycolysisYehong Han0Xueqin Deng1Haixia Chen2Jie Chen3Wei Xu4Lanqin Liu5Department of General Surgery, Hangzhou TCM Hospital affiliated to Zhejiang Chinese Medical UniversityDepartment of General Surgery, Hangzhou TCM Hospital affiliated to Zhejiang Chinese Medical UniversityDepartment of General Surgery, Hangzhou TCM Hospital affiliated to Zhejiang Chinese Medical UniversityDepartment of General Surgery, Hangzhou TCM Hospital affiliated to Zhejiang Chinese Medical UniversityDepartment of General Surgery, Hangzhou TCM Hospital affiliated to Zhejiang Chinese Medical UniversityDepartment of General Neurology, Hangzhou TCM Hospital affiliated to Zhejiang Chinese Medical UniversityAbstract Background Aerobic glycolysis is a hallmark of cancers including liver hepatocellular carcinoma (LIHC). RNA m5C methylation is involved in LIHC progression. However, the effect of a m5C writer, NSUN5, on glycolysis in LIHC remains not known. The present study aimed to investigate the effect of NSUN5 on glycolysis in LIHC and the molecular mechanism. Methods NSUN5 and EFNA3 expression data were acquired from The Cancer Genome Atlas database. Cell viability and glycolysis were evaluated. Tumor growth was evaluated using the xenograft tumor model. The effect of NSUN5 on EFNA3 m5C methylation was evaluated using methylated RNA immunoprecipitation and dual-luciferase reporter assay. Results We found that NSUN5 and EFNA3 expression was increased in LIHC and related to poor survival. Knocking down NSUN5 inhibited LIHC cell viability and glycolysis in vitro, and inhibited tumor growth and glycolysis in vivo. Moreover, the expression of NSUN5 was positively correlated with that of EFNA3. NSUN5 stabilized EFNA3 by promoting m5C modification of EFNA3. Additionally, overexpression of EFNA3 reversed the inhibition of cell viability and glycolysis induced by NSUN5 silence. Conclusion Silencing of NSUN5 decelerates LIHC progression by inhibiting glycolysis mediated by EFNA3 with m5C modification, highlighting the potential of NSUN5 as a therapeutic target for LIHC.https://doi.org/10.1186/s12885-025-14714-8Liver hepatocellular carcinomaNSUN5GlycolysisM5C methylationEFNA3
spellingShingle Yehong Han
Xueqin Deng
Haixia Chen
Jie Chen
Wei Xu
Lanqin Liu
NSUN5 accelerates the progression of liver hepatocellular carcinoma by m5C-EFNA3-mediated glycolysis
BMC Cancer
Liver hepatocellular carcinoma
NSUN5
Glycolysis
M5C methylation
EFNA3
title NSUN5 accelerates the progression of liver hepatocellular carcinoma by m5C-EFNA3-mediated glycolysis
title_full NSUN5 accelerates the progression of liver hepatocellular carcinoma by m5C-EFNA3-mediated glycolysis
title_fullStr NSUN5 accelerates the progression of liver hepatocellular carcinoma by m5C-EFNA3-mediated glycolysis
title_full_unstemmed NSUN5 accelerates the progression of liver hepatocellular carcinoma by m5C-EFNA3-mediated glycolysis
title_short NSUN5 accelerates the progression of liver hepatocellular carcinoma by m5C-EFNA3-mediated glycolysis
title_sort nsun5 accelerates the progression of liver hepatocellular carcinoma by m5c efna3 mediated glycolysis
topic Liver hepatocellular carcinoma
NSUN5
Glycolysis
M5C methylation
EFNA3
url https://doi.org/10.1186/s12885-025-14714-8
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