NSUN5 Facilitates Hepatocellular Carcinoma Progression by Increasing SMAD3 Expression
Hexu Han1, Chengcheng Zhang2, Wenbo Shi3
1Department of Gastroenterology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, 225300, P. R. China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|November 12, 2024
Summary
Hepatocellular carcinoma (HCC) progression is driven by NOP2/Sun RNA methyltransferase 5 (NSUN5), an oncogene that promotes metastasis. NSUN5 facilitates epithelial-mesenchymal transition (EMT) by regulating histone methylation, offering potential therapeutic targets for HCC.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Hepatocellular carcinoma (HCC) frequently metastasizes, leading to poor patient outcomes.
- Epithelial-mesenchymal transition (EMT) is a key driver of HCC metastasis.
- The role of NOP2/Sun RNA methyltransferase 5 (NSUN5) in HCC and EMT is largely unknown.
Purpose of the Study:
- To investigate the expression and function of NSUN5 in hepatocellular carcinoma.
- To elucidate the mechanism by which NSUN5 influences HCC metastasis and EMT.
- To determine if NSUN5 acts as an oncogene in HCC.
Main Methods:
- Clinicopathological analyses of multiple HCC cohorts.
- Tumor formation studies in Nsun5-knockout mice.
- In vitro and in vivo assays assessing cell invasion and migration.
- Mechanistic studies involving histone methylation (H3K4me3) and protein interactions (WDR5).
Main Results:
- NSUN5 expression is upregulated in HCC tumor tissues.
- Nsun5 deficiency hinders HCC progression, invasion, and migration.
- NSUN5 overexpression enhances EMT, invasion, and migration.
- NSUN5 promotes H3K4me3 enrichment at the SMAD3 promoter via WDR5, driving SMAD3-mediated EMT.
Conclusions:
- NSUN5 is significantly upregulated in HCC and acts as an oncogene promoting metastasis.
- NSUN5 drives HCC metastasis by facilitating EMT through the SMAD3 pathway.
- NSUN5 represents a novel therapeutic target for combating HCC metastasis.
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