MiR-34a suppresses HNSCC growth through modulating cell cycle arrest and senescence

Abstract

MiR-34a acts as a tumor suppressor in various malignancies. In HNSCC, the role of miR-34a in proliferation has not been fully elaborated and the target genes are still bind. Here, we addressed that forced miR-34a expression induced cell cycle arrest and senescence. Hypoxia/HIF1α was found to negatively correlate to the expression of miR-34a in HNSCC tissues and partially reverse miR-34a-imposed cell senescence through suppressing miR-34a expression. In order to screen the possible target genes of miR-34a in HNSCC, the differential genes mediated by miR-34a were screened by mRNA microarray. There were 91 genes co-down regulated in two cell lines, which were closely associated with MAPK, ErbB and p53 pathways. Genes, including FUT1, AXL, and MAP2K1 were finally identified as the novel targets of miR-34a by qPCR and luciferase assay. These findings indicate that miR-34a plays an essential role in suppressing HNSCC growth through inducing cell cycle arrest and senescence, by targeting proliferation-associated genes.