Histones Methyltransferase NSD3 Inhibits Lung Adenocarcinoma Glycolysis Through Interacting with PPP1CB to Decrease...

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Histone methyltransferase NSD3 (Nuclear Receptor SET Domain Containing 3) is frequently altered in cancers.
• The role of NSD3 in cancer initiation and progression is not fully understood.

Purpose of the Study:

• To investigate the function of NSD3 in lung adenocarcinoma.
• To elucidate the mechanism by which NSD3 affects cancer progression.

Main Methods:

• In vivo studies in lung adenocarcinoma models.
• Analysis of NSD3 expression correlation with clinical features and survival.
• Investigation of NSD3's effect on glycolysis, proliferation, migration, and invasion.
• Protein-protein interaction studies involving NSD3, PPP1CB, and p-STAT3.
• Assessment of environmental factors (CO2, pH) on protein phosphorylation.

Main Results:

• Downregulated NSD3 levels correlate with poor prognosis in lung adenocarcinoma.
• NSD3 inhibits tumor proliferation, migration, and invasion in vivo.
• NSD3 suppresses glycolysis by reducing HK2 translation and glucose uptake.
• NSD3 forms a complex with PPP1CB and p-STAT3 to dephosphorylate p-STAT3, inhibiting HK2 transcription.
• PPP1CB phosphorylation is influenced by CO2 and pH levels.

Conclusions:

• NSD3 plays a critical non-epigenetic role in suppressing lung adenocarcinoma.
• NSD3 regulates STAT3-dependent glycolysis through the NSD3/PPP1CB/p-STAT3 pathway.
• Targeting the NSD3/PPP1CB/p-STAT3 axis presents a potential therapeutic strategy for lung adenocarcinoma.