NUCB2 inhibition antagonizes osteosarcoma progression and promotes anti-tumor immunity through inactivating...

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Nucleobindin2 (NUCB2) is implicated in various cancers, but its role in osteosarcoma is unclear.
• Understanding NUCB2's function is crucial for developing targeted osteosarcoma therapies.

Purpose of the Study:

• To elucidate the biological functions and regulatory mechanisms of NUCB2 in osteosarcoma.
• To investigate NUCB2's role in metabolic stress response and tumor progression.
• To explore NUCB2's impact on the tumor immune microenvironment.

Main Methods:

• Assessed NUCB2 expression under glucose deprivation.
• Utilized NUCB2 depletion in vitro and in vivo models of osteosarcoma.
• Investigated downstream signaling pathways including CXCL8 and PD-L1.
• Examined the interaction between NUCB2 and NUCKS1.
• Evaluated combined NUCB2 depletion and anti-PD-L1 therapy.

Main Results:

• NUCB2 expression increased under glucose deprivation, suppressing cell death and ROS.
• NUCB2 depletion reduced osteosarcoma cell proliferation and metastasis.
• NUCB2 ablation decreased CXCL8 and PD-L1 expression, enhancing anti-tumor T-cell immunity.
• NUCB2 stabilized NUCKS1, promoting CXCL8 transcription.
• Combined NUCB2 depletion and anti-PD-L1 therapy improved anti-tumor immunity.

Conclusions:

• NUCB2 promotes osteosarcoma progression and an immunosuppressive microenvironment.
• NUCB2 exerts its function via the NUCKS1/CXCL8 pathway.
• Targeting NUCB2, potentially combined with immunotherapy, represents a promising strategy for osteosarcoma treatment.