15417786mcr190463-sup-221635_2_supp_5893400_q0tfts.pdf (289.74 kB)
Supplementary Fig. S3 from Hepatitis B Virus X Protein Induces RHAMM-Dependent Motility in Hepatocellular Carcinoma Cells via PI3K–Akt–Oct-1 Signaling
journal contributionposted on 2023-04-03, 17:02 authored by Yu-Chin Liu, Li-Feng Lu, Chia-Jung Li, Nian-Kang Sun, Jing-You Guo, Ya-Hui Huang, Chau-Ting Yeh, Chuck C.-K. Chao
The validation of HBx, Oct-1, and RHAMM expression on xenografts by IHC.
National Yang Ming University, Taipei, Taiwan
Chang Gung University, Taoyuan, Taiwan
Taiwan Animal Consortium
Ministry of Science and Technology of Taiwan
ARTICLE ABSTRACTChronic hepatitis B virus (HBV) infection is a major risk factor for the development of hepatocellular carcinoma (HCC), which represents one of the most common cancers worldwide. Recent studies suggest that HBV's protein X (HBx) plays a crucial role in HCC development and progression. Earlier, genome-wide analysis identified that the receptor for hyaluronan-mediated motility (RHAMM) represents a putative oncogene and is overexpressed in many human cancers, including HCC. However, the mechanism underlying RHAMM upregulation and its role in tumorigenesis remain unclear. Here, we show that ectopic expression of HBx activates the PI3K/Akt/Oct-1 pathway and upregulates RHAMM expression in HCC cells. HBx overexpression leads to dissociation of C/EBPβ from the RHAMM gene promoter, thereby inducing RHAMM upregulation. RHAMM knockdown attenuates HBx-induced cell migration and invasion in vitro. In mice, HBx promotes cancer cell colonization via RHAMM upregulation, resulting in enhanced metastasis. Analysis of gene expression datasets reveals that RHAMM mRNA level is upregulated in patients with HCC with poor prognosis. These results indicate that RHAMM expression is upregulated by HBx, a process that depends on the inhibition of C/EBPβ activity and activation of the PI3K/Akt/Oct-1 pathway. These results have several implications for the treatment of HBV-positive HCC involving upregulation of RHAMM and cancer metastasis. http://mcr.aacrjournals.org/content/molcanres/18/3/375/F1.large.jpg.
BiomarkersMetastasis biomarkersDrug TargetsCell surface receptor drug targetsEnvironmental Risk FactorsViral infectionGastrointestinal CancersLiver cancerGene RegulationTranscriptional control of cell differentiationProgression, Invasion & MetastasisCell adhesion and extracellular matrixViral OncogenesisDNA tumor virusesViral transformation and carcinogenesis