MicroRNAs (
miRNAs) are small non-coding RNAs that posttranscriptionally regulate gene expression during many biological processes. Recently, the aberrant expressions of
miRNAs have become a major focus in
cancer research. The purpose of this study was to identify deregulated
miRNAs in
oral cancer and further focus on specific
miRNAs that were related to patient survival. Here, we report that
miRNA expression profiling provided more precise information when
oral squamous cell carcinomas were subcategorized on the basis of clinicopathological parameters (
tumor primary site, histological subtype,
tumor stage, and HPV16 status). An innovative radar chart analysis method was developed to depict subcategories of
cancers taking into consideration the expression patterns of multiple
miRNAs combined with the clinicopathological parameters. Keratinization of
tumors and the high expression of miR-21 were the major factors related to the poor prognosis of patients. Interestingly, a majority of the keratinized
tumors expressed high levels of miR-21. Further investigations demonstrated the regulation of the tumor suppressor gene reversion-inducing
cysteine-rich
protein with kazal motifs (RECK) by two keratinization-associated
miRNAs, miR-7 and miR-21. Transfection of miR-7 and miR-21-mimics reduced the expression of RECK through direct
miRNA-mediated regulation, and these
miRNAs were inversely correlated with RECK in CAL 27 orthotopic xenograft
tumors. Furthermore, a similar inverse correlation was demonstrated in CAL 27 cells treated in vitro by different external stimuli such as trypsinization, cell density, and serum concentration. Taken together, our data show that keratinization is associated with poor prognosis of
oral cancer patients and keratinization-associated
miRNAs mediate deregulation of RECK which may contribute to the aggressiveness of
tumors.