Head and neck squamous cell carcinoma (HNSCC) is a prevalent disease worldwide, and the survival of HNSCC has not improved significantly over the last few decades. MicroRNAs (miRNAs) have an important regulatory role during carcinogenesis. Our study investigated the pathogenic implications of miR-134 in head and neck carcinogenesis. The clinicopathologic implications of miR-134 in HNSCC were investigated using expression assays and the functional role of miR-134 in HNSCC pathogenesis was determined using ectopic expression, knockdown and reporter assay experiments. Xenographic tumorigenesis and orthotopic nodal metastasis were assayed in mouse models. In situ hybridization and immunohistochemistry were used to detect the expression of miR-134 and the WWOX gene in human HNSCC. The results indicated that miR-134 was upregulated in HNSCC tissues relative to control mucosa. High expression of miR-134 was associated with nodal metastasis and mortality of patients. Decreased plasma miR-134 levels after tumor ablation indicated a better prognosis for patients. Multivariate analysis showed that high miR-134 expression in HNSCC was an independent predictor of poor survival. Ectopic miR-134 expression significantly enhanced in vitro oncogenic phenotypes and the orthotopic growth and metastasis of HNSCC cells. miR-134 targeted WW domain-containing oxidoreductase (WWOX) gene and cell invasion enhanced by miR-134 expression was abrogated by ectopic WWOX expression in HNSCC cells. miR-134 expression was reversely associated with the WWOX expression in HNSCC tissues. Evidences from our study substantiated that miR-134 expression contributes to head and neck carcinogenesis by targeting the WWOX.MicroRNAs (miRNAs) are 20-22 nucleotide, small, nonprotein-coding RNA molecules that negatively regulate the expression of target genes via epigenetic regulation.
Melanoma antigen (MAGE) family genes are frequently over-expressed in a subset population of multiple cancers, and serve as idea therapeutic targets; however, their distribution pattern in gastric cancers has not yet been evaluated. In this study, we first performed a cancer outlier profile analysis (COPA) on a series of public gene expression datasets of gastric cancer, and identified MAGEA12 showing a significant outlier expression model reproducibly. We further in silico validated that MAGEA12 outlier over-expression were associated with poor clinical outcome using six microarray datasets from GEO database. We then experimentally detected the MAGEA12 expression in an independent cohort of gastric cancer samples by immunohistochemistry, and showed that over-expression of MAGEA12 in a subset of cancers was associated with later stage and reduced survival; furthermore, MAGEA12 was an independent prognostic factor in an outlier manner. Our results indicate that MAGEA12 is a novel prognostic outlier gene in gastric cancers and patterns of MAGE expression may inform individualized targeted immunotherapies.
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