The role of ANP32B as a biomarker and therapeutic target in head and neck cancer

Abstract

<h3>Introduction</h3> Acidic leucine-rich nuclear phosphoprotein 32 family member B (ANP32B) is involved in gene expression, apoptosis, cell proliferation, and cell cycle progression. The role of this protein in head and neck squamous cell carcinoma (HNSCC) pathogenesis is not yet known. <h3>Materials and methods</h3> Biopsy specimens were analyzed from patients with HNSCC, oral cavity dysplasia, and benign tumors using miRNA TaqMan assays and quantitative polymerase chain reaction (n=45). Additionally, a luciferace reporter assay, loss of function and gain of function studies, and The Cancer Genome Atlas (TCGA) were used to perform analyses of gene expression data in relation with clinical data and survival outcomes. <h3>Results</h3> micro-RNA analysis of patients with HNSCC and controls showed an increase in miRNA1-2 expression in patients with oral cancer (P<0.05). A luciferase reporter assay showed the role of miRNA 1-2 in the post translational regula- tion of ANP32B expression. Loss of function and gain of function studies showed a mechanistic role of the miRNA 1-2-ANP32B axis in carcinogenesis and AKT phosphorylation in HNSCC cell lines. Analysis of the Cancer Genome Atlas (TCGA) data showed a significant increase of ANP32B expression in head and neck cancer patients (P<0.05). Levels of ANP32B expression were significantly higher in stage 2-4 compared to stage 1 of HNSCC. Males with head and neck cancer showed a significantly higher expression of ANP32B compared to females (P<0.05). No differential expression of ANP32B between different races was found. ANP32B expression was significantly associated with a higher grade of tumor (P-trend<0.05). Higher expression of ANP32B was found in N3 and N2 metastasis stages versus N1. High expression of ANP32B in females was associated with the poorest prognosis (P<0.05). <h3>Conclusions</h3> Altogether, our findings suggest that ANP32B acts as an oncogene in HNSCC and can be used as a potential thera- peutic target for HNSCC treatment.