Aberrant microRNA expression is a common phenotype in cancer cell progression. MicroRNA is the negative regulator of hundred to thousand gene expressions. Here we report chr14q32.2 miRNA cluster significantly down-regulated in clinical OSCC samples. 19 miRNAs were found with coordinated silencing in OSCC patients. However, their specific target and regulation mechanism have not clearly identified. Here we showed miR-376c is the most significant microRNA down-regulated by RT-Q-PCR validation in the miRNA cluster. Ectopic expression of miR-376c not only inhibited oral cancer cells proliferation, but also migration and invasion. MiR-376c also inhibited the in vivo tumorigenesis and metastasis. Furthermore, miR-376c was found directly binding to the 3'-UTR of oncogenic transcription factor, RUNX2, which was found significantly up-regulated in OSCC patients. Silencing of RUNX2 inhibited OSCC proliferation and invasion through INHBA expression. Taken together, our study demonstrates the tumor suppressor role of miR-376c, which regulates RUNX2 transcriptomes in OSCC. Moreover, our results indicate RUNX2-INHBA axis may play important roles in OSCC progression.
Date:
2015-04
Relation:
FASEB Journal. 2015 Apr;29(1, Suppl.):Abstract number 417.4.
