title: Overexpression of JARID1B promotes differentiation via SHIP1/AKT signaling in human hypopharyngeal squamous cell carcinoma.
abstract: Histone H3 (H3K4) demethylase JARID1B is aberrantly upregulated in many types of tumor and has been proposed to function as oncogene. Here we show that JARID1B is elevated in moderate and high-differentiated human hypopharyngeal squamous cell carcinoma (HPSCC) compared with low-differentiated HPSCC. Overexpression of JARID1B in FaDu cells increased epithelial differentiation marker K10 expression and inhibited cell proliferation. JARID1B and K10 mRNA expression is high correlated in HPSCC patients. Mechanistically, we found JARID1B directly bound to PI3K/AKT signaling inhibitor SHIP1 gene promoter and decreased SHIP1 gene expression. Activation of downstream AKT resulted in increased β-catenin signaling, by which promoted target genes Fra-1 and Jun, together with other AP-1 transcription factors, leading to K10 expression. Forced expression of SHIP1 rescued JARID1B-induced phenotypes on FaDu cell differentiation and proliferation. Taken together, our findings provide first evidence that elevated expression of JARID1B has a critical role in promoting HPSCC differentiation and inhibiting proliferation, suggesting JARID1B may function as a tumor suppressor in squamous cell cancers and implying a novel important therapeutic strategy of HPSCC.
authors: Key Laboratory, Department of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China.
authors: Jisheng
authors: J
authors: Zhang
authors: Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, 155 Han Zhong Road, Nanjing 210029, China.
authors: Xiaofei
authors: X
authors: An
authors: Key Laboratory, Department of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China.
authors: Yafei
authors: Y
authors: Han
authors: Department of Nephrology, Affiliated Hospital of Qingdao University, Qingdao 266 003, China.
authors: Rui
authors: R
authors: Ma
authors: Key Laboratory, Department of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China.
authors: Kun
authors: K
authors: Yang
authors: Key Laboratory, Department of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China.
authors: Lu
authors: L
authors: Zhang
authors: Key Laboratory, Department of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China.
authors: Jingwei
authors: J
authors: Chi
authors: Key Laboratory, Department of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China.
authors: Wei
authors: W
authors: Li
authors: Institute of Genetic Medicine-Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
authors: David
authors: D
authors: Llobet-Navas
authors: Department of Nephrology, Affiliated Hospital of Qingdao University, Qingdao 266 003, China.
authors: Yan
authors: Y
authors: Xu
authors: Key Laboratory, Department of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China.
authors: Yan
authors: Y
authors: Jiang
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D053550:Keratin-10 / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010641:Phenotype; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D051176:beta Catenin / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D012097:Repressor Proteins; D051176:beta Catenin; D053550:Keratin-10; D056484:Jumonji Domain-Containing Histone Demethylases; C119611:KDM5B protein, human; D051057:Proto-Oncogene Proteins c-akt; C000606430:INPP5D protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases