Chromobox Homolog 4 is Positively Correlated to Tumor Growth, Survival and Activation of HIF-1α Signaling in Human Osteosarcoma under Normoxic Condition

Abstract

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.

CBX4 promotes the proliferation and metastasis via regulating BMI‐1 in lung cancer

“…CBX4 expression varies in different types of cancer and has diverse biological functions. It is a cell cycle promoting gene with proliferative activity and is found in the epithelium; this protein is found to be up‐regulated and exhibits pro‐tumour effect by activating the HIF‐1α signalling pathway in osteosarcoma . In our study, we demonstrated that the expression of CBX4 in lung tumour tissues was significantly higher compared with adjacent cancer tissues (Figure A,B).…”

“…It is a cell cycle promoting gene with proliferative activity and is found in the epithelium; this protein is found to be up-regulated and exhibits pro-tumour effect by activating the HIF-1α signalling pathway in osteosarcoma. 16,22,23 In our study, we demonstrated that the expression of CBX4 in lung tumour tissues was significantly higher compared with adjacent cancer tissues ( Figure 1A,B). Meanwhile, higher CBX4 expression was positively correlated with tumour size, clinical stage and lymph node metastasis (Table 1).…”

“…Recently, evidence has revealed that CBX4 is a cell cycle inhibitor gene of proliferative activity in the epithelium . Under normoxic conditions, CBX4 acts as an up‐regulated protein with a pro‐tumour effect by activating the HIF‐1α signalling pathway in osteosarcoma . In addition, CBX4 is a new therapeutic target for hepatocellular carcinoma, as high expression of this protein leads to poor overall survival .…”

“…22 Under normoxic conditions, CBX4 acts as an up-regulated protein with a pro-tumour effect by activating the HIF-1α signalling pathway in osteosarcoma. 23 In addition, CBX4 is a new therapeutic target for hepatocellular carcinoma, as high expression of this protein leads to poor overall survival. 17,24 In general, researchers proved that CBX4 plays an important role in the occurrence and development of tumours.…”

CNOT1 cooperates with LMNA to aggravate osteosarcoma tumorigenesis through the Hedgehog signaling pathway

“…Knockdown of CNOT1 could inhibit Hedgehog signaling pathway. Activation of the Hedgehog signaling pathway has been implicated in the development of many human malignancies, including prostate cancer (Xu et al, 2014), ovarian cancer (Li et al, 2016), and breast cancer (Zhou et al, 2016). Overexpression of LMNA could rescue CNOT1 knockdown-mediated tumor inhibition and Hedgehog signaling pathway inhibition.…”