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Published on: July 20, 2014
Clinical and Functional Characterization of CD-NTase Enzymes in Esophageal Squamous Cell Carcinoma
Zhiwen Gong1,2, Hongcheng Zhong1, Shijiancong Liu1
1Department of Thoracic Surgery, The Fifth Affiliated Hospital, Sun Yat-sen Unversity, Zhuhai 519000, China.
Abstract:
Purpose: The cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzyme family plays a critical role in tumor development, but its clinical significance and biological function in esophageal squamous cell carcinoma (ESCC) remain unclear. Methods: We analyzed 352 ESCC cases, including 260 from public datasets (TCGA, GSE53624, and GSE53622) and 92 from our clinical cohort. Candidate CD-NTase enzymes were validated through in vivo and in vitro experiments. Results: Analysis of 11 CD-NTase enzymes identified MB21D2 as the only significant prognostic factor in three clinical cohorts. Patients with low MB21D2 expression demonstrated markedly worse overall survival (OS). Multivariate analysis indicated that low MB21D2 was an independent prognostic factor (HR = 2.5, P =0.04; HR = 1.33, P =0.02; HR = 2.5, P =0.02). Furthermore, biological functional experiments showed that knockdown MB21D2 promotes proliferation, migration, and invasion in ESCC cells. While overexpression MB21D2 has the opposite effect. RNA-seq and western blotting analysis revealed that knockdown of MB21D2 activates markers associated with the Wnt/β-catenin signaling pathway, thereby promoting ESCC progression. Conclusion: MB21D2 serves as a critical prognostic and functional factor in ESCC progression, offering a potential therapeutic target for improving patient outcomes.
Insights
MB21D2 is a key prognostic factor in esophageal squamous cell carcinoma (ESCC). Low MB21D2 expression worsens survival and promotes tumor progression, identifying it as a potential therapeutic target for ESCC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzyme family is implicated in tumor development.
- The specific role of CD-NTase enzymes in esophageal squamous cell carcinoma (ESCC) is not well understood.
Purpose of the Study:
- To investigate the clinical significance and biological function of CD-NTase enzymes in ESCC.
- To identify potential prognostic biomarkers and therapeutic targets for ESCC.
Main Methods:
- Analysis of 352 ESCC cases from public datasets and a clinical cohort.
- Validation of candidate CD-NTase enzymes using in vivo and in vitro experiments.
- RNA-sequencing and western blotting to elucidate molecular mechanisms.
Main Results:
- MB21D2 was identified as the sole significant prognostic factor among 11 CD-NTase enzymes.
- Low MB21D2 expression correlated with significantly worse overall survival in ESCC patients.
- Knockdown of MB21D2 promoted ESCC cell proliferation, migration, and invasion, while overexpression had the opposite effect.
- MB21D2 knockdown activated the Wnt/β-catenin signaling pathway, driving ESCC progression.
Conclusions:
- MB21D2 is a critical prognostic and functional factor in ESCC progression.
- MB21D2 represents a potential therapeutic target for improving outcomes in ESCC patients.
