Downregulation of NUDT21 contributes to cervical cancer progression through alternative polyadenylation

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Nudix Hydrolase 21 (NUDT21) is an alternative polyadenylation (APA) regulatory protein with known tumor-suppressive functions.
• The specific role of NUDT21 in cervical cancer (CxCa) pathogenesis has not been previously elucidated.

Purpose of the Study:

• To investigate the expression levels and functional role of NUDT21 in cervical cancer.
• To determine the impact of NUDT21 on CxCa cell behavior and tumor progression.
• To identify molecular mechanisms underlying NUDT21's function in CxCa.

Main Methods:

• Quantitative analysis of NUDT21 expression in CxCa tissues and cells.
• In vitro and in vivo experiments involving NUDT21 knockdown and overexpression.
• Polyadenylation site sequencing (PAS-Seq) to identify APA site changes.
• Analysis of signaling pathways (Wnt, NF-κB) and metabolic gene expression.

Main Results:

• NUDT21 expression is significantly reduced in CxCa tissues and cells, correlating with poor patient prognosis.
• NUDT21 knockdown enhances CxCa cell proliferation, migration, invasion, tumorigenesis, and lung metastasis.
• NUDT21 overexpression reverses these pro-tumorigenic effects.
• PAS-Seq revealed 457 transcripts with lengthened 3' UTRs upon NUDT21 overexpression.
• NUDT21 modulates genes involved in fatty acid metabolism and Wnt/NF-κB signaling pathways.

Conclusions:

• NUDT21 functions as a crucial tumor suppressor in cervical cancer.
• NUDT21 regulates CxCa progression through APA-dependent modulation of gene expression, impacting key signaling pathways.
• NUDT21 represents a potential therapeutic target for cervical cancer treatment.