title: Loss of miR-125b-1 contributes to head and neck cancer development by dysregulating TACSTD2 and MAPK pathway.
abstract: MicroRNAs (miRNAs) have important roles in the initiation and progression of human cancer, but their role in head and neck cancer development and progression is not well defined. We aimed to determine whether specific miRNAs and their target mRNAs contribute to head and neck cancer pathogenesis and progression. To identify miRNAs associated with head and neck squamous cell carcinomas (HNSCCs), we analyzed HNSCC cell lines, normal head and neck tissues and normal keratinocytes by miRNA profiling; a group of differentially expressed miRNAs was identified, which includes miR-125b. Decreased expression of miR-125b is known to occur in epithelial cancers and many target mRNAs for this miR have been reported. We found decreased expression of miR-125b-1 and hypermethylation of its promoter in HNSCC compared with its non-malignant counterpart. The TACSTD2 (also known as TROP2) gene was identified and validated as a direct target of miR-125b-1. Abnormal expression of TACSTD2 cell-surface glycoprotein has been reported in most epithelial tumors, and the overexpressions of this mRNA and protein product has been considered a useful tumor marker. We report that miR-125b-1 causes mitogen-activated protein kinase pathway dysfunction through regulation of TACSTD2 expression. Thus, loss of miR-125b-1 may have a key role in the pathogenesis and progression of squamous cell carcinomas of head and neck and possibly of other tumors.
authors: Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA.
authors: H
authors: H
authors: Nakanishi
authors: Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA.
authors: C
authors: C
authors: Taccioli
authors: Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA.
authors: J
authors: J
authors: Palatini
authors: Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA.
authors: C
authors: C
authors: Fernandez-Cymering
authors: Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA.
authors: R
authors: R
authors: Cui
authors: Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA.
authors: T
authors: T
authors: Kim
authors: Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA.
authors: S
authors: S
authors: Volinia
authors: Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA.
authors: C M
authors: CM
authors: Croce
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D000077195:Squamous Cell Carcinoma of Head and Neck; D015854:Up-Regulation
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; C499380:TACSTD2 protein, human; D020928:Mitogen-Activated Protein Kinases