Purpose: Hepatocellular carcinoma (HCC) is the most common malignant tumor worldwide with high morbidity and mortality rates. We aimed to examine the expression of chromobox 6 (CBX6) in HCC and analyze its correlation with clinicopathological features of HCC patients. Moreover, the role of CBX6 in the HCC cell proliferation, invasion and metastasis and the potential mechanism underlying HCC metastasis were also investigated.
Methods: We used quantitative polymerase chain reaction (qRT-PCR) and Western blot to evaluate the expression levels of CBX6 in HCC cell lines. Furthermore, the expression of CBX6 in HCC and the adjacent non-tumor tissues was assessed by immunohistochemistry (IHC). Cell proliferation was evaluated using MTT assay, cell migration and invasion were measured using wound healing and transwell assays. Finally, we detected the expression of target proteins in HCC cell lines transfected with CBX6 overexpression plasmid or CBX6 shRNA plasmid by Western blot.
Results: We found that the expression of CBX6 was increased in 280 cases of HCC tissues compared that in adjacent non-tumor tissues. HCC patients with high CBX6 expression had a higher tendency to have high growth rate, strong invasion ability, high clinical stage and poor tumor differentiation. Functional study demonstrated that the upregulation of CBX6 promotes proliferation, migration and invasion of HCC cells while silencing CBX6 in HCC cells significantly inhibited cell proliferation, migration and invasion. Furthermore, CBX6 could accelerate the EMT process in HCC cells by upregulating the expression of snail and zeb1.
Conclusion: CBX6 played an important role in the process of tumorigenesis and progression in HCC and enhanced the invasion and metastasis ability of HCC cells through regulating transcription factors snail/zeb1-mediated EMT mechanism, which indicated that the protein could serve as a novel therapeutic target for the treatment of HCC.
Keywords: CBX6, HCC, metastasis, EMT