Abstract
BackgroundThe function of hornerin (HRNR), a member of the S100 protein family, is poorly clarified in the development of human tumors. The role of HRNR in hepatocellular carcinoma (HCC) progression is investigated in the study.MethodsThe expression levels of HRNR were assessed in tumor samples from a cohort of 271 HCC patients. The effect of HRNR on proliferation, colony formation and invasion of tumor cells was examined. We further determined the role of HRNR in tumor growth in vivo by using xenograft HCC tumor models. The possible mechanism of the HRNR promotion of HCC progression was explored.ResultsWe found that HRNR was overexpressed in HCC tissues. The high expression of HRNR in HCCs was significantly associated with vascular invasion, poor tumor differentiation, and advanced TNM stage. The disease-free survival (DFS) and overall survival (OS) of HCC patients with high HRNR expression were poorer than those in the low HRNR expression group. HRNR expression was an independent risk factor linked to both poor DFS (HR = 2.209, 95% CI = 1.627–2.998,P < 0.001) and OS (HR = 2.459,95% CI = 1.736–3.484, P < 0.001). In addition, the knockdown of HRNR by shRNAs significantly inhibited the proliferation, colony formation, migration and invasion of HCC tumor cells. HRNR silencing led to the decreased phosphorylation of AKT signaling. Notably, tumor growth was markedly inhibited by HRNR silencing in a xenograft model of HCC.ConclusionsHRNR promotes tumor progression and is correlated with a poor HCC prognosis. HRNR may contribute to HCC progression via the regulation of the AKT pathway.
Highlights
The function of hornerin (HRNR), a member of the S100 protein family, is poorly clarified in the development of human tumors
HRNR expression is related with poor prognosis of hepatocellular carcinoma (HCC) To explore the role of HRNR in HCC, we analyzed the expression of HRNR in tumor samples from a cohort of 271 HCC patients
The results revealed that high HRNR expression in HCC positively correlated with vascular invasion (P = 0.002), poor tumor differentiation (P = 0.042) and advanced TNM stage (P < 0.001); the high expression of HRNR in HCCs had no significant correlation with age, gender, HCC family history, hepatitis B, liver function Child-Pugh stage, cirrhosis, tumor size, tumor number, encapsulation and alpha-fetoprotein (AFP) (Table 1)
Summary
The function of hornerin (HRNR), a member of the S100 protein family, is poorly clarified in the development of human tumors. The role of HRNR in hepatocellular carcinoma (HCC) progression is investigated in the study. The gene of hornerin gene (HRNR) is clustered on the chromosome region 1q21 [2]. This gene was first discovered in the mouse embryo epidermis, and was detected in the skin, tongue, oesophagus and proximal stomach of adult mice. HRNR was reported to be involved in breast cancer development and malignant transformation [8]. The purpose of the study was to define the expression levels of HRNR in HCC patients and its involvement in HCC progression
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