Expression and prognostic role of ubiquitination factor E4B in primary hepatocellular carcinoma

Abstract

Ubiquitination factor E4B (UBE4B) has been speculated to have contradictory functions upon tumorigenesis as an oncogene or tumor suppressor in different types of cancers. We investigated the expression and prognostic role of UBE4B in primary hepatocellular carcinoma (HCC) using cell lines and 149 archived HCC samples. Correlation between the functions of UBE4B in HCC was also explored. We used human HCC cell lines (HepG2, Hep3B, SK-Hep1, Huh7, SMMC-7721, BEL-7402) and a normal hepatocyte cell line (LO2) along with HCC samples from patients who had undergone resection for HCC previously at our hospital. A battery of methods (real-time quantitative polymerase chain reaction; Western blotting; immunohistochjemical analyses; cell proliferation and colony formation assays; cell migration and cell invasion assays) were employed to assess various aspects of UBE4B.We found that UBE4B expression was upregulated aberrantly at mRNA and protein levels in human primary HCC tissues. Amplified expression of UBE4B was highly correlated with poor outcome. Silencing of UBE4B expression by siRNA inhibited the proliferation, colony formation, migration and invasion of HCC cells in vitro, and resulted in significant apoptosis that was associated with downregulation of expression of Bcl-2 and upregulation of expression of total p53, p-p53, Bax and Cleaved-Caspase3 in HCC cells. Our findings suggested that UBE4B might have an oncogenic role in human primary HCC, and that it could be used as a prognostic marker (as well as a potential molecular target) for the treatment of HCC.

<p>The Roles of Ubiquitination Factor E4B (UBE4B) in the Postoperative Prognosis of Patients with Renal Cell Carcinoma and in Renal Tumor Cells Growth and Metastasis</p>

“…Similarly, our previous research had reported the relation between the magnifying expression of UBE4B and unfavorable prognosis in HCC. 24 Conversely, studies by Zage et al 31 and Sarah et al 32 reported that low UBE4B expression was related to an unfavorable prognosis in patients with neuroblastoma. These findings implied that UBE4B might act as a new prognostic indicator for patients with various malignancies.…”

“…Several studies had reported similar cellular functions of UBE4B in various types of solid cancers. 21,23,24,35 Weng et al 23 discovered that reduction of UBE4B expression could suppress Nasopharyngeal carcinoma cell growth. Zhang et al 24 reported that lowering UBE4B expression by siRNA suppressed the growth and mobility ability of HCC cells.…”

“…23 Our previous study also demonstrated that UBE4B overexpression promoted the tumorigenesis of hepatocellular carcinoma (HCC) and was related to a poor outcome in HCC patients. 24 As far as we know, the expression and prognostic value of UBE4B in tumorigenesis of RCC has not been clarified yet.…”

Early Diagnosis of Hepatocellular Carcinoma Using Machine Learning Method

“…For instance, LAMC1 mRNA can promote the development of HCC by competing with miR-124 and supporting the excretion of CD151 (Yang et al, 2017). UBE4B can be used as a potential prognostic marker for HCC treatment due to its carcinogenic effect in human primary HCC (Zhang et al, 2016). Additionally, HNF1A is closely associated with HCC because the number of HNF1A increase when non-cancerous liver develops into high differentiate HCC (Wang et al, 1998).…”

Reversal of the multidrug resistance of human ileocecal adenocarcinoma cells by acetyl-11-keto-β-boswellic acid <i>via</i> downregulation of P-glycoprotein signals

“…Supernatants were collected and protein concentration was determined using the Bradford assay (19). Samples containing 50 µg of protein were subjected to 10% SDS-PAGE and electro-transferred to nitrocellulose membranes that were blocked with 3% non-fat milk/0.1% Tween 20/TBS, 100 mM NaCl in 10 mM Tris, pH 7.5, incubated with anti-P-gp antibody (sc-13131, Santa Cruz, CA, USA) for 1 h at room temperature followed by horseradish-peroxidase-conjugated secondary antibody for another 1 h at room temperature.…”