NSUN6 Promotes Gastric Cancer Progression by Stabilizing CEBPZ mRNA in a m⁵C-Dependent Manner

Area of Science:

• Molecular Oncology
• Epigenetics
• RNA Modifications

Background:

• Gastric cancer (GC) is a significant global health concern, arising from gastric mucosa epithelial cells.
• RNA modifications, such as 5-methylcytosine (m⁵C), play crucial roles in gene regulation and cancer development.
• The specific role of NSUN6 in GC and its regulatory mechanisms remain largely unexplored.

Purpose of the Study:

• To investigate the function of NOL1/NOP2/SUN domain (NSUN)6 in gastric cancer (GC).
• To elucidate the molecular mechanisms by which NSUN6 influences GC progression.
• To identify NSUN6 as a potential therapeutic target in GC treatment.

Main Methods:

• In vitro experiments using human gastric mucosa and GC cell lines.
• Quantification of m⁵C levels using dot blot analysis.
• Assessment of cell viability, proliferation, and apoptosis using CCK-8, colony formation, and flow cytometry assays.
• Detection of autophagy-related proteins via Western blot and validation of NSUN6-CEBPZ interaction using RNA immunoprecipitation.

Main Results:

• NSUN6 was identified as an oncogene promoting GC progression.
• NSUN6 inhibition decreased GC cell proliferation and induced apoptosis and autophagy.
• NSUN6 enhanced CCAAT/Enhancer Binding Protein Zeta (CEBPZ) mRNA stability through m⁵C methylation, suppressing autophagy via the p53/mTOR pathway.

Conclusions:

• NSUN6 promotes gastric cancer progression by stabilizing CEBPZ mRNA via m⁵C modification.
• Targeting NSUN6 may offer a novel therapeutic strategy for gastric cancer.
• Further in vivo and clinical studies are necessary to validate these findings and their translational potential.