CBX8 exhibits oncogenic properties and serves as a prognostic factor in hepatocellular carcinoma

Abstract

Polycomb group family is a class of proteins that have important roles in both physiological and pathological processes, and its family member Chromobox homolog 8 (CBX8) regulates cell differentiation, aging, and cell cycle progression in numerous carcinomas; however, the effects and underlying mechanisms of CBX8 in hepatocellular carcinoma (HCC) are rarely reported. We found that CBX8 expression in clinical HCC specimens correlates inversely with patient survival. In HCC cells, we found that enforced overexpression of CBX8 induces epithelial–mesenchymal transition, invasive migration, and stem cell-like traits, which are associated with increased tumor growth and metastasis in mice. Conversely, CBX8 silencing inhibits the aggressive phenotype of HCC cells that have high CBX8 expression. Mechanistically, CBX8 modulates H3K27me3 in the gene promoter of bone morphogenetic protein 4 (BMP4), which is associated with active BMP4 transcription and, consequently, the activation of Smads and mitogen-activated protein kinases. BMP4 expression reverses the effects of CBX8 silencing in inhibiting epithelial–mesenchymal transition, stemness, and metastasis. Our results establish CBX8 as a critical driver of HCC stem cell-like and metastatic behaviors and characterize its role in modulating BMP4 expression. These findings have implications for the targeting of CBX8 as an approach to HCC prognosis and treatment.

RETRACTED ARTICLE: Correlations between chromobox homolog 8 and key factors of epithelial–mesenchymal transition in hepatocellular carcinoma

“…Moreover, recent studies have shown that CBX8 was deregulated in several kinds of tumors including HCC. CBX8 was over-expressed in HCC tissues and correlated with poor prognosis of patients [14, 15]. Mechanistically, CBX8 activates bone morphogenetic protein 4 (BMP4) transcription by modulating H3K27me3 [15].…”

“…CBX8 was over-expressed in HCC tissues and correlated with poor prognosis of patients [14, 15]. Mechanistically, CBX8 activates bone morphogenetic protein 4 (BMP4) transcription by modulating H3K27me3 [15]. In addition, CBX8 could efficiently activate AKT/β-catenin signaling via up-regulation of the transcription factor EGR1 and miR-365-3p [14].…”

“…CBX8 has been found up-regulated in human esophageal carcinoma, colorectal cancer and HCC [12–14]. Moreover, CBX8 is considered as an oncogene and prognostic marker in HCC [15].…”

Chromobox homolog 8 (CBX8) Interacts with Y-Box binding protein 1 (YBX1) to promote cellular proliferation in hepatocellular carcinoma cells

“…Dysregulation of CBX8 has been reported in various human cancers [15, 16, 20–22, 24]. Growing research has shown the cell proliferation promoting effects of CBX8 in different types of cancers [15, 18, 20].…”

“…Zhang’s and Bo Tang’s reports are consistent with our results and have further confirmed the reliability of our results. However, the mechanisms of malignant HCC progression are different [18, 22]. We first found a new important binding partner for CBX8, and found that CBX8 regulates the proliferation of HCC cells through the regulation of cell cycle pathways.…”