Identification of miR-143 as a tumour suppressor in nasopharyngeal carcinoma based on microRNA expression profiling.

Recent evidence has indicated that miRNAs play important roles in carcinogenesis. The identification of dysregulated miRNAs and the target genes they regulate might enhance our understanding of the molecular mechanisms of nasopharyngeal carcinoma (NPC). A microarray analysis was performed to identify dysregulated miRNAs in NPC tissue samples, and protein-coding genes targeted by three or more downregulated miRNAs were selected using miRWalk and used in a pathway enrichment analysis. Nineteen KEGG pathways were selected by DAVID, including the MAPK, focal adhesion, gap junction, ECM-receptor interaction, TGF-beta, and p53 signalling pathways, most of which are involved in NPC carcinogenesis and progression. MiR-143 was significantly downregulated in NPC cell lines and clinical samples. The ectopic expression of miR-143 suppressed NPC cell viability, colony formation, and anchorage-independent growth in vitro, and it inhibited xenograft tumour growth in vivo. Furthermore, KRAS was confirmed as a direct target of miR-143, and silencing KRAS expression suppressed NPC cell viability and proliferation. The miR-143/KRAS pathway provides new insight into the molecular mechanisms that regulate the development and progression of NPC, and it provides novel therapeutic targets for NPC.