Strand-specific miR-28-3p and miR-28-5p have differential effects on nasopharyngeal cancer cells proliferation, apoptosis, migration and invasion.

ABSTRACT

BACKGROUND: MicroRNAs (miRNAs) play crucial roles in varieties of cancers, particularly in tumorigenesis, progression, and migration. Dysregulation of miR-28 was reported to occur in various types of human malignancies. In humans, two different mature miRNA sequences are excised from opposite arms of the stem-loop pre-miR-28, hsa-miR-28-3p and hsamiR-28-5p. However, the expression and distinct role of miR-28-3p and miR-28-5p in nasopharyngeal carcinoma (NPC) remain undetermined. METHODS: The expressions of miR-28-3p/-5p in human NPC tissues were tested by quantitative real-time PCR. miR-28-3p/-5p were overexpressed by mimics and silenced by inhibitors. The roles of miR-28-3p/-5p in NPC development were studied using cultured HONE-1 cells. RESULTS: The mRNA expression levels of miR-28-3p and -5p were significantly decreased in NPC tissues in comparison with adjacent normal tissues. Overexpression of miR-28-5p suppressed NPC cell proliferation and induced cell cycle arrest and apoptosis, while miR-28-3p promoted NPC cell migration and invasion. The miRNAs effected on different signal pathways miR-28-5p altered expression of cyclin D1 and influenced the PI3K/AKT signaling pathway. In contrast, miR-28-3p downregulated Nm23-H1 and accelerated the process of EMT. CONCLUSION: miR-28-3p and -5p were both downregulated in NPC tissues but had distinct biological effects in NPC cells. They may serve as potential prognostic markers and therapeutic targets for NPC.