MicroRNA-378 functions as an onco-miR in nasopharyngeal carcinoma by repressing TOB2 expression

Abstract

Increasing evidence indicates that microRNAs (miRNAs) has been implicated in the progression and metastasis of numerous cancers. In particular, abnormal expression of miR-378 has been observed in various cancers and is associated with cell survival, migration, invasion, angio-genesis and tumor growth. Our previous studies have shown that miR-378 was decreased in nasopharyngeal carcinoma (NPC) plasma and was negatively correlated with NPC progression. However, the tissue expression of miR-378 and its biological function remained unknown in NPC. In this study, we report for the first time that expression level of miR-378 was commonly upregulated in both NPC tissues and NPC cell lines compared to normal healthy nasopharyngeal epithelial samples and human nasopharyngeal epithelial cell lines (NP69), respectively, and was opposite to the reported results in plasma. Functional studies showed that upregulation of miR-378 dramatically promoted cell proliferation, colony formation, migration and invasion in vitro, as well as tumor growth in vivo. Bioinformatics analyses were performed to predict the target genes of miR-378, and the following mechanistic investigations revealed that miR-378 overexpression was able to downregulate the expression of transducer of ERBB2 (TOB2), a potential tumor suppressor, and miR-378 silencing enhanced TOB2 expression. In clinical specimens, TOB2 was widely repressed in tumor tissues accompanied by miR-378 overexpression. Taken together, this study indicates that miR-378 regulates TOB2 and may function as an onco-miR in NPC progression, providing a potential target for gene therapy of NPC.