Abstract
Down-regulation of tumor-suppressive miR-145 has been reported in various malignancies, including oral squamous-cell carcinoma (OSCC) that is influenced by several factors, including Epstein-Barr virus (EBV) and human papillomavirus (HPV). Oncoviruses can modulate the expression of cellular microRNAs. Therefore, we sought to investigate the association of miR-145 down-regulation in OSCC with EBV and/or HPV infection, which might be a possible mechanism of these viruses in oral carcinogenesis. Herein, prevalence of EBV, HPV, and their co-infection was significantly higher in tumors than normal tissues of OSCC. EBV infection alone or jointly with HPV was significantly associated with down-regulation of miR-145 in tumors compared with normal adjacent tissues. In cell lines infected with EBV or HPV, miR-145 was also down-regulated. Consistently, methylation of miR-145 was significantly greater in tumors, and well correlated with increased expression of DNMT3B, which was influenced by infection with EBV and HPV. In cell lines, only EBV infection was associated with increased expression of DNMT3B. Moreover, the level of EBV-LMP1 mRNA in tumors was negatively correlated with miR-145 and positively correlated with DNMT3B. Therefore, EBV alone or jointly with HPV is associated with down-regulation of miR-145 and may influence on miR-145 promoter methylation through the induction of DNMT3B in OSCC.
Highlights
Oral squamous-cell carcinoma (OSCC) is the most common subtype of head and neck squamous-cell carcinoma (HNSCC) and the most frequently occurring malignancy in the oral cavity, representing more than 90% of all cancer types at this anatomical site
MiR-145 was down-regulated in Epstein-Barr virus (EBV)-positive cells when compared with EBV-negative cells (Figure 3C). These results demonstrate that EBV and human papillomavirus (HPV) infection dysregulate the expression of miR-145 in OSCC
We examined whether EBV and HPV are associated with down-regulation of miR-145 in a range of cancer cell lines
Summary
Oral squamous-cell carcinoma (OSCC) is the most common subtype of head and neck squamous-cell carcinoma (HNSCC) and the most frequently occurring malignancy in the oral cavity, representing more than 90% of all cancer types at this anatomical site. 300,000 new OSCC cases are diagnosed annually [1,2]. Development of OSCC is influenced by various risk factors, such as tobacco smoking, alcohol consumption, and betel quid chewing [3]. Epstein-Barr virus (EBV), is considered a risk factor for OSCC [4,5]. The incidence of EBV- and HPV-associated OSCC has been increasing recently. Joint infection with EBV and HPV is an important etiologic factor of this cancer [6]. HPV-positive OSCC tissues are often co-infected with EBV [7]. In contrast to HPV, it remains unclear whether EBV has a role in OSCC pathogenesis, and little is known about the pathogenesis of OSCC in cases of joint infection with EBV and HPV
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