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Transcriptomic identification of key genes influencing m7G modification in thyroid carcinoma and experimental
Bo Li1,2, Liying Zhu3, Jiewu Zhang4
1Department of Head and Neck Surgery, Harbin Medical University Cancer Hospital, No.150 Haping Road, Nangang District, Harbin, 150040, Heilongjiang, China.
Background:
N7-methylguanosine (m7G) modification plays a critical role in RNA metabolism and is increasingly recognized for its implications in cancer biology. It can influence RNA stability, translation efficiency, and gene expression regulation. However, the specific role of m7G modification and its downstream genes in thyroid carcinoma (THCA) is not well understood. To comprehensively explore the impact of m7G methylation modification and the m7G-related gene ZNF831 on THCA, this study aims to identify key genes influencing m7G modification in THCA, with a particular focus on clarifying the role of ZNF831. This study is expected to further elucidate the pathological mechanisms of THCA and fill the current research gap in this field.
Methods:
Weighted gene co-expression network (WGCNA) analysis was used to evaluate the expression of m7G-related genes in the THCA expression data from the GEO (Gene Expression Omnibus) datasets. Machine learning algorithms, including the least absolute shrinkage and selection operator (LASSO), gradient boosting decision tree (XGBoost), and random forest (RF), were used to identify the feature genes, including GPSM3 and ZNF831, in the TCGA-THCA dataset. Immunohistochemistry was used to identify the expression difference of ZNF831 in 3 THCA tissues and 3 normal tissues. Finally, the changes of proliferation and migration of THCA cells after overexpression of ZNF831 were investigated.
Results:
This study investigated m7G-related genes in THCA, focusing on ZNF831 as a key tumor suppressor. Differential expression analysis revealed significant dysregulation of m7G-related genes in THCA. Functional and bioinformatics analyses, including gene set enrichment analysis and protein-protein interaction network construction, identified ZNF831 as a candidate gene. Experimental validation demonstrated that ZNF831 overexpression significantly reduced the proliferation and migration of THCA cells. Additionally, tumor microenvironment analysis showed a positive correlation between ZNF831 expression and immune cell infiltration, indicating its potential role in enhancing anti-tumor immunity.
Conclusions:
These findings underscore the importance of m7G modifications and m7G-related gene ZNF831 in THCA pathogenesis, highlighting their potential as therapeutic targets. Further research is needed to elucidate the molecular mechanisms and explore clinical applications of these findings.
Insights
N7-methylguanosine (m7G) modification and its related gene ZNF831 show potential as therapeutic targets in thyroid carcinoma (THCA). This study identified ZNF831 as a tumor suppressor that reduces THCA cell proliferation and migration.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- N7-methylguanosine (m7G) modification is crucial for RNA metabolism and increasingly linked to cancer biology.
- Its specific role and downstream genes in thyroid carcinoma (THCA) remain largely unexplored.
- Understanding m7G modification's impact on THCA is vital for advancing cancer research.
Purpose of the Study:
- To investigate the role of m7G modification and the m7G-related gene ZNF831 in thyroid carcinoma (THCA).
- To identify key genes influencing m7G modification in THCA.
- To elucidate the pathological mechanisms of THCA and ZNF831's function.
Main Methods:
- Weighted gene co-expression network analysis (WGCNA) on GEO datasets.
- Machine learning algorithms (LASSO, XGBoost, RF) to identify feature genes (GPSM3, ZNF831) in TCGA-THCA data.
- Immunohistochemistry and cell-based assays to validate ZNF831's role in THCA proliferation and migration.
Main Results:
- Significant dysregulation of m7G-related genes observed in THCA.
- ZNF831 identified as a key tumor suppressor gene.
- Overexpression of ZNF831 significantly inhibited THCA cell proliferation and migration.
- Positive correlation between ZNF831 expression and anti-tumor immune cell infiltration found.
Conclusions:
- m7G modifications and ZNF831 are important in THCA pathogenesis.
- ZNF831 demonstrates potential as a therapeutic target in THCA.
- Further research is warranted to explore molecular mechanisms and clinical applications.
