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

Lushan Xiao,Jin-Lin Hou,Li Liu,Jie Peng,Jingyuan Sun,Dong Zhongyi,Yang Song,Dehua Wu,Zixiao Zhou,Qingcan Sun,Hongbo Zhu,Hui-Chuan Cao,Wenwen Li

doi:10.18632/aging.102241

Abstract

Polycomb group (PcG) proteins have recently been identified as critical regulators in tumor initiation and development. However, the function of CBX8 in human hepatocellular carcinoma (HCC) remains largely unknown. Our study was designed to explore the biological function and clinical implication of CBX8 in HCC. We investigated the interplay between CBX8 and cell cycle through Gene Set Enrichment Analysis and western blotting. Bioinformatics tools and co-immunoprecipitation were used to explore cell cycle regulation. Finally, we studied the expression and clinical significance of CBX8 in HCC through 3 independent datasets. CBX8 was upregulated in HCC and its expression correlated with cell cycle progression. CyclinD1 was downregulated by CBX8 knockdown but upregulated by CBX8 overexpression. YBX1 interacted with CBX8 and regulated the cell cycle. Moreover, targeting YBX1 with specific siRNA impaired CBX8-mediated regulation of CyclinD1. CBX8 overexpression boosted HCC cell growth, while CBX8 knockdown suppressed cell proliferation. Further, YBX1 interacted with CBX8. YBX1 knockdown compromised the proliferation of CBX8 overexpressing cells. CBX8 promotes HCC cell proliferation through YBX1 mediated cell cycle progression and is related to poor HCC prognoses. Therefore, CBX8 may serve as a potential target for the diagnosis and treatment of HCC.

Highlights

Liver cancer was predicted to be the sixth most commonly diagnosed cancer and the fourth leading cause of cancer-related mortality worldwide in 2018, with about 841,000 new cases and 782,000 deaths annually [1]
To dissect the molecular mechanism of CBX8, we carried out Gene Set Enrichment Analysis (GSEA) of The Cancer Genome Atlas (TCGA) cohort and found that CBX8 high expressing groups were enriched for cell cycle-related gene sets (Figure 1A and 1B)
To confirm its function in regulating the cell cycle, we detected a series of cell cycle-related genes after interfering with CBX8 and found that CCND1 was significantly down-regulated (Figure 1D, Supplementary Figure 1A), and that CyclinD1 was downregulated by CBX8-knockdown at the protein level (Figure 1C)

Summary

Introduction

Liver cancer was predicted to be the sixth most commonly diagnosed cancer and the fourth leading cause of cancer-related mortality worldwide in 2018, with about 841,000 new cases and 782,000 deaths annually [1]. Hepatocellular carcinoma (HCC), accounting for most (75%–85%) of the primary liver www.aging-us.com cancers occurring worldwide, remains one of the most prevalent and deadliest human cancers [1]. Deregulation and dysfunction of PcG proteins often lead to blockade or inappropriate activation of developmental pathways, enhancement of cellular proliferation, inhibition of apoptosis, and restoration of the cancer stem cell population [7,8,9,10]. PcG proteins have been shown to exhibit non-polycomb functions, contributing to the regulation of diverse cellular functions [7, 12,13,14]. CBX8 has been demonstrated to exhibit oncogenic functions in a noncanonical manner in human malignancies. The mechanism by which CBX8 regulates the malignant growth of HCC remains unclear

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