Mechanisms by which chromobox homolog 4 regulates angiogenic mimicry and angiogenic activity in osteosarcoma.

Osteosarcoma (OS) is a very aggressive malignant neoplasm characterized by significant metastases and a deficiency of treatment targets. Therefore, it is urgent to find new therapeutic mechanisms and targets for OS. We assessed the capability of chromobox homolog 4 (CBX4) to modulate OS growth using in vivo and in vitro dual tests utilizing short hairpin RNA technology, 3-dimensional tumor sphere building, immunofluorescence co-localization, and other biotechnological methods. Our findings indicated that CBX4 was overexpressed in OS tissues, and the silencing of CBX4 markedly reduced OS cell proliferation, migration, and invasion. CBX4 modulates vasculogenic mimicry through its influence on yes1 associated transcriptional regulator (YAP1) and neuropilin-2/vascular endothelial growth factor A (NRP2/VEGFA) pathway, hence promoting angiogenic activity, a mechanism perhaps linked to CBX4's role in regulating mitochondrial autophagy. CBX4 affects vasculogenic mimicry by regulating the YAP1 and NRP2/VEGFA pathways and promotes the OS process. CBX4 may serve as a novel biomarker for OS, potentially offering innovative approaches for early diagnosis and tailored therapy of OS. SIGNIFICANCE STATEMENT: Osteosarcoma (OS) is a very aggressive malignant neoplasm characterized by significant metastases and a deficiency of treatment targets. Therefore, it is urgent to find new therapeutic mechanisms and targets for OS. Chromobox homolog 4 may serve as a novel biomarker for OS, potentially offering innovative approaches for early diagnosis and tailored therapy of OS.