Upregulation of EPS8L3 is associated with tumorigenesis and poor prognosis in patients with liver cancer

Abstract

epidermal growth factor receptor kinase substrate 8 (ePS8) plays critical roles in a variety of solid tumors. However, the biologic functions and clinical significance of ePS8-like 3 (ePS8l3), an ePS8-related protein, in liver cancer remain unclear. To measure ePS8l3 expression in liver cancer cell lines, reverse transcription-quantitative Pcr and western blot analyses were performed. The correlation between 338 patients with liver cancer and various clinicopathological factors obtained from the oncomine database were evaluated using the χ 2 test. Survival of patients with different expression of ePS8l3 was determined using Kaplan-Meier survival analysis with a log rank test, and cox regression analysis was performed to estimate the prognostic significance of EPS8L3 expression. additionally, cell proliferation and migration were determined using cell counting Kit-8 and wound healing assays. The results revealed that ePS8l3 expression was significantly upregulated in liver cancer tissues and cell lines (P<0.01), and that the expression of ePS8l3 was closely associated with grade (P=0.024) and mortality (P=0.011). Furthermore, survival analysis suggested patients with high ePS8l3 expression exhibited shorter survival compared with those with low ePS8l3 expression. cox regression analysis indicated that ePS8l3 could be regarded as a prognostic biomarker in patients with liver cancer (hazard ratio, 1.58; 95% confidence interval, 1.085-2.301; P=0.017). Additionally, in vitro assays revealed that EPS8L3 depletion significantly inhibited liver cancer cell proliferation and migration, and reduced the levels of phosphorylated Pi3K and aKT in the Pi3K/aKT signaling pathway. collectively, the results of the present study, for the first time to the best of our knowledge, demonstrated that ePS8l3 serves as an oncogene in liver cancer development; therefore, ePS8l3 may be a valuable prognostic predictor for patients with liver cancer.

Dissecting novel mechanisms of hepatitis B virus related hepatocellular carcinoma using meta-analysis of public data

“…Likewise, we observed upregulation of centromere protein F, helicase RAD54B, and topoisomerase TOP2A. We also found upregulation of the mitogen PBK, NEK2 (a regulator of mitotic progression), and the kinase TTK, all of which promote HCC cell proliferation and migration via Akt signaling[ 21 , 22 , 58 ]. Similarly, we found upregulation of minichromosome maintenance family (MCMs) members MCM2 and MCM10, which also promote cell division[ 59 - 61 ].…”

“…For example, glypican-3 (GPC3), a cell surface glycoprotein that interacts with Wnt/β-catenin, Yes associated protein, and Hedgehog pathways[ 20 ]. Additionally, Akt signaling was activated through the epidermal growth factor receptor kinase substrate 8-like protein 3, a substrate for the epidermal growth factor receptor[ 21 ]. Furthermore, we found upregulation of the serine/threonine kinase PDZ-binding kinase (PBK), a mitotic kinase related to mitogen-activated protein kinase kinase (MAPKK)[ 22 ].…”

Dissecting Novel Tumor Antigens and Immune Subtypes Guided mRNA Vaccine Development for HBV Related-Hepatocellular Carcinoma

“…For example, EPS8L3 has pivotal oncogenic functions in liver cancer, inhibition of EPS8L3 can prevent the progression of liver cancer and improve the e cacy of sorafenib treatment 20 . Furthermore, EPS8L3 depletion signi cantly inhibited cell proliferation and migration of liver cancer, and decreased the levels of phosphorylated PI3K and AKT in the PI3K/AKT signaling pathway 21 . TCOF1 expression is aberrantly elevated in HCC and correlates with progression and poor outcome 22 .…”

The role of molecular subtypes and immune infiltration characteristics based on disulfidptosis-associated genes in lung adenocarcinoma

“…EPS8L3 is involved in the regulation of various cellular processes, including cell growth, proliferation and survival [ 35 ]. Although not reported in LUAD, its upregulation is associated with tumorigenesis and poor prognosis in patients with liver cancer, and can be used as a potential therapeutic target [ 36 , 37 ].…”