1. Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No.600, Yishan Road, Shanghai, 200233, China;
2. Institute of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No.600, Yishan Road, Shanghai, 200233, China;
3. Department of Ultrasound, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No.600, Yishan Road, Shanghai, 200233, China.
* These authors contributed equally to this work.
Objectives: The clinical significance and tumorigenesis of Chromobox homolog 4 (CBX4) have been reported in hepatocellular carcinoma. The purpose of this study is to confirm the expression, elucidate the biological function and investigate the potential mechanism of CBX4 in osteosarcoma (OS). Methods: The expression of CBX4 in OS samples and cell lines was measured by RT-PCR and western blot test. Cell cycle, CCK8 and colony-forming assays were used to detect changes of cells growth. Cell apoptosis assay was used to measure cell survival capacity. Trans-well assay was used to test the activities of migration and invasion. The expression of genes regulated by CBX4 was detected by qRT-PCT test. Results: The expression of CBX4 was up-regulated in multiple OS cell lines and clinical samples. Overexpression of CBX4 was correlated with advanced clinical stage, high degree of malignancy and low tumor necrosis rate. Moreover, knockdown of CBX4 resulted in significant inhibition of cell growth and cell survival in OS cells under normoxic condition. In addition, we found that knockdown of CBX4 lead to down-regulating of HIF-1α-targeted genes without changing HIF-1α expression itself. Conclusion: Taken together, CBX4 is up-regulated and has a pro-tumor effect in OS with an activation of HIF-1α signaling pathway under normoxic condition. Therefore, targeting CBX4 may provide a new therapeutic method for OS.
Keywords: Chromobox homolog 4, Growth, Survival, HIF-1α pathway, Osteosarcoma.