The microRNA-processing enzymes: Drosha and Dicer can predict prognosis of nasopharyngeal carcinoma

Abstract

Dysregulation of microRNA (miRNA) metabolism has been observed in a variety of human cancers, but the expression patterns of the enzymes responsible for generating miRNAs remain largely unexplored. In this study, we investigated the expression profiles of the two most important enzymes of the miRNA machinery, Drosha and Dicer, which were closely correlated with nasopharyngeal carcinoma (NPC) and patient survival. Dicer and Drosha mRNA levels were detected by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) using 24 NPC tissues, 7 normal nasopharyngeal epithelium samples (NPE) and NPC cell lines. In addition, protein levels were detected by immunohistochemistry (IHC) using an NPC tissue microarray (TMA), which include 251 NPC and 105 NPE cases. For some NPC patients can not be contacted, the survival data were available only for 146 patients. Kaplan-Meier analysis was performed, and the chi-square and log-rank tests were used to detect significance levels using SPSS 15.0 software. The mean level of Dicer and Drosha mRNA were significantly down-regulated in NPC tissue specimens and cell lines when compared with controls. The low levels of Dicer and Drosha protein were frequently seen in NPC, and the low expression of Dicer and Drosha protein was significantly correlated with shorter progression-free survival (PFS) and overall survival (OS) of NPC patients. We observed that Drosha and Dicer expression was dysregulation in NPC compared with healthy control samples and was significantly correlated with shorter PFS and OS of NPC patients. Therefore, we hypothesise that the expression levels of Dicer and Drosha could be used as potential prognostic biomarkers for NPC.