Title Interleukin-17A promotes tongue squamous cell carcinoma metastasis through activating miR-23b/versican pathway
Authors Wei, Tai
Cong, Xin
Wang, Xiang-Ting
Xu, Xiao-Jian
Min, Sai-Nan
Ye, Peng
Peng, Xin
Wu, Li-Ling
Yu, Guang-Yan
Affiliation Peking Univ, Sch & Hosp Stomatol, Dept Oral & Maxillofacial Surg, Natl Engn Lab Digital & Mat Technol Stomatol, Beijing, Peoples R China.
Beijing Key Lab Digital Stomatol, Beijing, Peoples R China.
Peking Univ, Sch Basic Med Sci, Key Lab Mol Cardiovasc Sci, Dept Physiol & Pathophysiol,Minist Educ, Beijing, Peoples R China.
Beijing Key Lab Cardiovasc Receptors Res, Beijing, Peoples R China.
Univ Sci & Technol China, Sch Life Sci, Dept Cell & Dev Biol, Hefei, Peoples R China.
Peking Univ, Hosp 3, Dept Ophthalmol, Beijing, Peoples R China.
Peking Univ, Sch & Hosp Stomatol, Dept Oral & Maxillofacial Surg, Natl Engn Lab Digital & Mat Technol Stomatol, Beijing, Peoples R China.
Yu, GY (reprint author), Beijing Key Lab Digital Stomatol, Beijing, Peoples R China.
Wu, LL (reprint author), Peking Univ, Sch Basic Med Sci, Key Lab Mol Cardiovasc Sci, Dept Physiol & Pathophysiol,Minist Educ, Beijing, Peoples R China.
Wu, LL (reprint author), Beijing Key Lab Cardiovasc Receptors Res, Beijing, Peoples R China.
Keywords interleukin-17A
miR-23b
versican
tongue squamous cell carcinoma
metastasis
STROMAL VERSICAN EXPRESSION
CANCER CELLS
KAPPA-B
CLINICOPATHOLOGICAL FACTORS
PROTEOGLYCAN SYNTHESIS
CYTOKINE EXPRESSION
ANTITUMOR-ACTIVITY
PROSTATE-CANCER
BLADDER-CANCER
OVARIAN-CANCER
Issue Date 2017
Publisher ONCOTARGET
Citation ONCOTARGET.2017,8(4),6663-6680.
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-kappa B inhibited miR-23b transcription by directly binding to its promoter region. IL-17A downregulated miR-23b expression via activating NF-kappa B signaling pathway characterized by increasing p65 expression in the nuclear and elevating the levels of p-IKKa and p-I kappa Ba. 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.
URI http://hdl.handle.net/20.500.11897/475609
ISSN 1949-2553
DOI 10.18632/oncotarget.14255
Indexed SCI(E)
Appears in Collections: 口腔医院
基础医学院
第三医院

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