Objective We previously performed a meta-analysis of microRNA profiling studies on head and neck / oral cancer (HNOC), and identified 11 consistently dysregulated microRNAs in HNOC. Here, we evaluate the diagnostic values of these microRNAs in oral tongue squamous cell carcinoma (OTSCC) using oral cytology samples. Materials and Methods The levels of 11 microRNAs were assessed in 39 oral cytology samples (19 OTSCC and 20 normal subjects), and 10 paired OTSCC and adjacent normal tissues. The predictive power of these microRNAs was analyzed by receiver operating characteristic curve (ROC) and random forest (RF) model. A classification and regression trees (CART) model was generated using miR-21 and miR-375, and further validated using both independent oral cytology validation sample set (14 OTSCC and 11 normal subjects) and tissue validation sample set (12 paired OTSCC and adjacent normal tissues). Results Differential expression of miR-21, miR-100, miR-125b and miR-375 was validated in oral cytology training sample set. Based on the RF model, the combination of miR-21 and miR-375 was selected which provide best prediction of OTSCC. A CART model was constructed using miR-21 and miR-375, and was tested in both oral cytology and tissue validation sample sets. A sensitivity of 100% and specificity of 64% was achieved in distinguishing OTSCC from normal in the oral cytology validation set, and a sensitivity of 83% and specificity of 83% was achieved in the tissue validation set. Conclusion The utility of microRNA from oral cytology samples as biomarkers for OTSCC detection is successfully demonstrated in this study.

Background: Ameloblastomas are odontogenic neoplasms characterized by local invasiveness. This study was conducted to address the role of matrix metalloproteinase-2 (MMP-2) in the invasiveness of ameloblastomas.

The miR-99 family is one of the evolutionarily most ancient microRNA families, and it plays a critical role in developmental timing and the maintenance of tissue identity. Recent studies, including reports from our group, suggested that the miR-99 family regulates various physiological processes in adult tissues, such as dermal wound healing, and a number of disease processes, including cancer. By combining 5 independent genome-wide expression profiling experiments, we identified a panel of 266 unique transcripts that were down-regulated in epithelial cells transfected with miR-99 family members. A comprehensive bioinformatics analysis using 12 different sequence-based microRNA target prediction algorithms revealed that 81 out of these 266 down-regulated transcripts are potential direct targets for the miR-99 family. Confirmation experiments and functional analyses were performed to further assess 6 selected miR-99 target genes, including mammalian Target of rapamycin (mTOR), Homeobox A1 (HOXA1), CTD small phosphatase-like (CTDSPL), N-myristoyltransferase 1 (NMT1), Transmembrane protein 30A (TMEM30A), and SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 (SMARCA5). HOXA1 is a known proto-oncogene, and it also plays an important role in embryonic development. The direct targeting of the miR-99 family to two candidate binding sequences located in the HOXA1 mRNA was confirmed using a luciferase reporter gene assay and a ribonucleoprotein-immunoprecipitation (RIP-IP) assay. Ectopic transfection of miR-99 family reduced the expression of HOXA1, which, in consequence, down-regulated the expression of its downstream gene (i.e., Bcl-2) and led to reduced proliferation and cell migration, as well as enhanced apoptosis. In summary, we identified a number of high-confidence miR-99 family target genes, including proto-oncogene HOXA1, which may play an important role in regulating epithelial cell proliferation and migration during physiological disease processes, such as dermal wound healing and tumorigenesis.