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NOP2-mediated m5C methylation of XPD is associated with hepatocellular carcinoma progression

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Guo-Fang Sun,  Hao Ding

Abstract:

Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality. Our previous study has confirmed that XPD acts as an anti-oncogene and is downregulated in HCC. The mechanism of XPD downregulation in HCC is unclear. In this work, we obtained the datasets related to HCC patients from GSE76427, LIRI-JP, and TCGA-LIHC cohorts. Among 15 m5C regulators (NSUN2, NSUN3, NSUN4, NSUN5, NSUN6, NSUN7, DNMT1, TRDMT1, DNMT3A, DNMT3B and NOP2, TET1, TET2, and TET3, ALYREF), 14 m5C regulators were upregulated in tumor tissues of HCC patients, except for TET2. HCC patients were divided into Cluster A and B with different m5C methylation patterns. Cluster B was enriched in metabolism-related signaling pathways, and Cluster A was prominently associated with the cell cycle signaling pathway. Moreover, XPD was positively correlated with NOP2. Cluster B exhibited upregulation of XPD and had an obvious survival advantage with respect to Cluster A. Additionally, NOP2 and XPD were downregulated in HCC tumors and cells. In vitro assays revealed that NOP2 overexpression enhanced XPD expression by elevating the m5C methylation of XPD, which contributed to inhibit proliferation, migration, and invasion of HCC cells. In conclusion, this work demonstrated that XPD mRNA stability was elevated by NOP2-mediated m5C methylation modification and then inhibited the malignant progression of HCC, suggesting that XPD may be a potential target for HCC treatment.

Received date: 01/10/2023

Accepted date: 05/09/2023

Ahead of print publish date: 06/30/2023

Issue: 3/2023

Volume: 70

Pages: 340 — 349

Keywords: XPD, m5C methylation, NOP2, hepatocellular carcinoma

Supplementary files:
N17 Suppl Figure Legends-TE1.docx
N17 Suppl FigS1-TE1.tif

DOI: 10.4149/neo_2023_230110N17

Pubmed

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