CBX1 Indicates Poor Outcomes and Exerts Oncogenic Activity in Hepatocellular Carcinoma

Abstract

Dysregulation of chromobox proteins contributes to the progression of human diseases. CBX1 has been implicated in epigenetic control of chromatin structure and gene expression, but its role in human cancers remains largely unknown. Here we show that CBX1 exhibits oncogenic activities in hepatocellular carcinoma (HCC) and indicates poor outcomes. The expression of CBX1 was noticeably increased, at both mRNA and protein levels, in HCC tissues and cell lines, compared with the nontumorous ones. High CBX1 expression was significantly associated with larger tumor size, poor tumor differentiation and tumor vascular invasion. Patients with elevated expression of CBX1 were frequently accompanied with unfavorable overall and disease-free survivals in two independent cohorts consisting of 648 HCC cases. The prognostic value of CBX1 was further confirmed by stratified survival analyses. Multivariate cox regression model suggested CBX1 as an independent factor for overall survival (hazard ratio = 1.735, 95% confident interval: 1.342–2.244, P < .001). In vitro data demonstrated that CBX1 overexpression promoted cell proliferation and migration, whereas the knockdown of CBX1 resulted in the opposite phenotypes. Mechanistically, CBX1 interacted with transcription factor HMGA2 to activate the Wnt/β-Catenin signaling pathway. Suppression of β-Catenin by siRNA or specific inhibitor XAV-939 markedly attenuated CBX1-mediated cell growth. Collectively, our findings indicate that CBX1 functions as an oncogene and may serve as a potential prognostic biomarker in HCC.

The Prognostic Value of the Chromobox Family in Human Ovarian Cancer

“…Yang et al [12] also discovered that CBX1 protein expression was dramatically upregulated in HCC. It was suggested that HCC patients with elevated levels of CBX1 had shorter survival times and tumor recurrence times [12]. Recently, Liang et al [27] revealed that high expression of CBX1 might be predictive for poor clinical outcomes in breast cancer, especially in estrogen receptor-positive patients.…”

“…One study indicated that CBX1 was a key regulator in regulating cell differentiation and proliferation, and silencing CBX1 inhibited prostate cancer cell proliferation [26]. Yang et al [12] also discovered that CBX1 protein expression was dramatically upregulated in HCC. It was suggested that HCC patients with elevated levels of CBX1 had shorter survival times and tumor recurrence times [12].…”

“…Biologically, CBX1 knockdown inhibited prostate cancer cell proliferation by triggering cell cycle arrest in the G1 phase, indicating that CBX1 was positively related to cancer cell proliferation [29]. In vitro data indicated that overexpressed CBX1 activated the Wnt/β-catenin signaling pathway through the transcription factor HMGA2, thus promoting HCC cell growth and migration [12]. Knockdown of CBX1 or inhibition of β-catenin markedly reduced the CBX1-mediated cell growth in HCC [12].…”

“…For example, the CBX3 protein is commonly upregulated in human colorectal cancer and promotes cancer cell proliferation both in vitro and in vivo [11]. Immunohistochemistry-based clinicopathological studies showed that the expression of the CBX1 protein was significantly elevated in human hepatocellular carcinoma (HCC) specimens [12], and CBX2 protein expression was elevated in human prostate cancer tissues [13], predicting a poor outcome in these patients. Conversely, Wang et al revealed that the CBX8 protein inhibits the metastasis of esophageal squamous cell carcinoma by suppressing Snail expression [14].…”

VCAN – A novel prognostic marker for gastric cancer

“…Elevated expression of VCAN predicted worse outcomes for patients as shorter survival times were observed in the high expression group compared with the low expression group. Again, previous evidence had documented the associations between upregulated gene expressions and poor patients outcome (41)(42)(43)(44) and VCAN had been reported as an unfavorable prognostic marker in oral squamous cell carcinoma and endometrial cancer (11,45). VCAN expression in gastric cancer may be a potential diagnostic tool and a marker of poor outcome for patients.…”