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Updated: Oct 20, 2025

SUMO-Binding Entities SUBEs as Tools for the Enrichment, Isolation, Identification, and Characterization of the SUMO Proteome in Liver Cancer
Published on: November 1, 2019
NSUN2 modified by SUMO-2/3 promotes gastric cancer progression and regulates mRNA m5C methylation
Yuanbo Hu1,2, Chenbin Chen1,2, Xinya Tong2
1Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Abstract:
The 5-methylcytosine (m5C) RNA methyltransferase NSUN2 is involved in the regulation of cell proliferation and metastasis formation and is upregulated in multiple cancers. However, the biological significance of NSUN2 in gastric cancer (GC) and the modification of NSUN2 itself have not been fully investigated. Here, we analyzed the expression level of NSUN2 in tissue microarrays containing 403 GC tissues by immunohistochemistry. NSUN2 was upregulated in GC, and that it was a predictor of poor prognosis. NSUN2 promotes the proliferation, migration, and invasion of GC cells in vitro. We also demonstrated that small ubiquitin-like modifier (SUMO)-2/3 interacts directly with NSUN2 by stabilizing it and mediating its nuclear transport. This facilitates the carcinogenic activity of NSUN2. Furthermore, m5C bisulfite sequencing (Bis-seq) in NSUN2-deficient GC cells showed that m5C-methylated genes are involved in multiple cancer-related signaling pathways. PIK3R1 and PCYT1A may be the target genes that participate in GC progression. Our findings revealed a novel mechanism by which NSUN2 functions in GC progression. This may provide new treatment options for GC patients.
Insights
The RNA methyltransferase NSUN2 is upregulated in gastric cancer (GC), promoting tumor growth and metastasis. Its modification by SUMO-2/3 enhances its carcinogenic activity, offering potential new GC treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- The 5-methylcytosine (m5C) RNA methyltransferase NSUN2 is implicated in cancer progression.
- Its specific role and modifications in gastric cancer (GC) remain underexplored.
Purpose of the Study:
- To investigate the biological significance and regulatory mechanisms of NSUN2 in gastric cancer.
- To identify potential therapeutic targets for GC treatment.
Main Methods:
- Immunohistochemistry analysis of NSUN2 expression in 403 GC tissues.
- In vitro assays to assess the effects of NSUN2 on GC cell proliferation, migration, and invasion.
- Co-immunoprecipitation to study NSUN2-SUMO-2/3 interaction.
- m5C bisulfite sequencing (Bis-seq) in NSUN2-deficient GC cells.
Main Results:
- NSUN2 is upregulated in GC and predicts a poor prognosis.
- NSUN2 overexpression enhances GC cell proliferation, migration, and invasion.
- Small ubiquitin-like modifier (SUMO)-2/3 directly interacts with NSUN2, stabilizing it and promoting its nuclear transport, thereby enhancing its carcinogenic activity.
- m5C-methylated genes, including potential targets PIK3R1 and PCYT1A, are involved in GC progression.
Conclusions:
- NSUN2 plays a significant role in GC progression through promoting cell proliferation, migration, and invasion.
- SUMOylation of NSUN2 is a key mechanism regulating its function and localization in GC.
- Targeting NSUN2 or its modification pathways may offer novel therapeutic strategies for gastric cancer.
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