RRC ID 62723
Author Aiyama T, Orimo T, Yokoo H, Ohata T, Hatanaka KC, Hatanaka Y, Fukai M, Kamiyama T, Taketomi A.
Title Adenomatous polyposis coli-binding protein end-binding 1 promotes hepatocellular carcinoma growth and metastasis.
Journal PLoS One
Abstract This study was performed to determine the clinical significance of adenomatous polyposis coli (APC)-binding protein end-binding 1 (EB1) in hepatocellular carcinoma (HCC) and to characterize its biochemical role in comparison with previous reports. We performed immunohistochemical staining to detect EB1 expression in tissues from 235 patients with HCC and investigated its correlations with clinicopathological features and prognosis. We also investigated the roles of EB1 in cell proliferation, migration, and tumorigenesis in vitro and in vivo by siRNA- and CRISPR/Cas9-mediated modulation of EB1 expression in human HCC cell lines. The results showed that EB1 expression was significantly correlated with several important factors associated with tumor malignancy, including histological differentiation, portal vein invasion status, and intrahepatic metastasis. Patients with high EB1 expression in HCC tissue had poorer overall survival and higher recurrence rates than patients with low EB1 expression. EB1 knockdown and knockout in HCC cells reduced cell proliferation, migration, and invasion in vitro and inhibited tumor growth in vivo. Further, genes encoding Dlk1, HAMP, and SLCO1B3 that were differentially expressed in association with EB1 were identified using RNA microarray analysis. In conclusion, elevated expression of EB1 promotes tumor growth and metastasis of HCC. EB1 may serve as a new biomarker for HCC, and genes coexpressed with EB1 may represent potential targets for therapy.
Volume 15(9)
Pages e0239462
Published 2020-1-1
DOI 10.1371/journal.pone.0239462
PII PONE-D-20-12629
PMID 32956413
PMC PMC7505586
MeSH Adult Aged Animals Carcinoma, Hepatocellular / complications Carcinoma, Hepatocellular / genetics Carcinoma, Hepatocellular / pathology* Cell Differentiation Cell Line, Tumor Cell Proliferation Female Gene Expression Regulation, Neoplastic Gene Knockout Techniques Genes, APC Hepatitis, Viral, Human / complications Heterografts Humans Kaplan-Meier Estimate Liver Neoplasms / complications Liver Neoplasms / genetics Liver Neoplasms / pathology* Male Mice, Inbred BALB C Mice, Nude Microtubule-Associated Proteins / antagonists & inhibitors Microtubule-Associated Proteins / genetics Microtubule-Associated Proteins / physiology* Middle Aged Neoplasm Invasiveness Neoplasm Metastasis Neoplasm Proteins / antagonists & inhibitors Neoplasm Proteins / genetics Neoplasm Proteins / physiology* Portal Vein / pathology Prognosis RNA Interference RNA, Messenger / biosynthesis RNA, Messenger / genetics RNA, Neoplasm / biosynthesis RNA, Neoplasm / genetics RNA, Small Interfering / genetics Recombinant Proteins / metabolism Recurrence Survival Rate Tissue Array Analysis
IF 2.74
Human and Animal Cells Li-7(RCB1941)