title: Interleukin-17A promotes tongue squamous cell carcinoma metastasis through activating miR-23b/versican pathway.
abstract: Interleukin-17A (IL-17A), a proinflammatory cytokine mainly produced by T helper 17 cells, exerts protumor or antitumor effects in different cancer entities. However, the exact role of IL-17A in carcinogenesis and progression of tongue squamous cell carcinoma (TSCC) remains unclear. Here, we found that the levels of IL-17A in serum and tumor samples were significantly increased in TSCC patients and positively correlated with tumor metastasis and clinical stage. Besides, IL-17A enhanced cell migration and invasion in SCC15, a TSCC cell line. Furthermore, IL-17A inversely correlated with miR-23b expression in TSCC specimens. In vitro, NF-κB inhibited miR-23b transcription by directly binding to its promoter region. IL-17A downregulated miR-23b expression via activating NF-κB signaling pathway characterized by increasing p65 expression in the nuclear and elevating the levels of p-IKKα and p-IκBα. Overexpression of miR-23b inhibited, whereas knockdown of miR-23b promoted migration and invasion abilities of SCC15 cells. Moreover, extracellular matrix protein versican was proved to be the direct target of miR-23b through luciferase assay. IL-17A increased versican levels in vitro and knockdown of versican by siRNA inhibited SCC15 cell migration and invasion. Taken together, these results reveal a novel mechanism that IL-17A in TSCC microenvironment promotes the migration and invasion of TSCC cells through targeting miR-23b/versican pathway.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, and Beijing Key Laboratory of Digital Stomatology, Beijing, China.
authors.forename: Tai
authors.initials: T
authors.lastname: Wei
authors.affiliation: Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, and Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Cong
authors.affiliation: Department of Cell and Developmental Biology, School of Life Science, University of Science and Technology of China, Hefei, China.
authors.forename: Xiang-Ting
authors.initials: XT
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Peking University Third Hospital, Beijing, China.
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Xu
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, and Beijing Key Laboratory of Digital Stomatology, Beijing, China.
authors.forename: Sai-Nan
authors.initials: SN
authors.lastname: Min
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, and Beijing Key Laboratory of Digital Stomatology, Beijing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Ye
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, and Beijing Key Laboratory of Digital Stomatology, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, and Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, China.
authors.forename: Li-Ling
authors.initials: LL
authors.lastname: Wu
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, and Beijing Key Laboratory of Digital Stomatology, Beijing, China.
authors.forename: Guang-Yan
authors.initials: GY
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D001665:Binding Sites; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D020381:Interleukin-17 / Q000097:blood / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D013997:Time Factors; D014062:Tongue Neoplasms / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051996:Transcription Factor RelA / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D059016:Tumor Microenvironment; D053675:Versicans / Q000235:genetics / Q000378:metabolism*
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; C552430:MIRN23a microRNA, human; D035683:MicroRNAs; C000606204:NFKBIA protein, human; C498143:RELA protein, human; D051996:Transcription Factor RelA; C508322:VCAN protein, human; D053675:Versicans; D000072000:NF-KappaB Inhibitor alpha; C496559:CHUK protein, human; D051550:I-kappa B Kinase
keywords: interleukin-17A; metastasis; miR-23b; tongue squamous cell carcinoma; versican