Epstein-Barr Virus Infection Alone or Jointly with Human Papillomavirus Associates with Down-Regulation of miR-145 in Oral Squamous-Cell Carcinoma

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.