title: Globular adiponectin inhibits leptin-stimulated esophageal adenocarcinoma cell proliferation via adiponectin receptor 2-mediated suppression of UHRF1.
abstract: Esophageal adenocarcinoma (EAC) is one of the most common malignancies in the world which is associated the increased prevalence of obesity. In the context of obesity, leptin can directly contribute to progression of EAC. Adiponectin inhibits leptin-induced oncogenic signaling in EAC cells. However, the exact molecular mechanisms linking obesity, adipokines, and EAC remain far from completely understood. In the present study, we tested the role of ubiquitin-like with PHD and ring finger domains 1 (UHRF1) in adiponectin-induced protective effects against leptin-induced EAC cell proliferation. We found that globular adiponectin (gAD) significantly inhibited leptin-induced increase of cell proliferation and decrease of apoptosis in OE 19 cells. Moreover, leptin-induced increase of UHRF1 expression was suppressed by gAD. Compared with normal controls, UHRF1 expression was markedly increased in EAC tissues and cell lines. Silence of UHRF1 increased the expression of cleaved caspase 3 and 9 and Bax, reduced the expression of Bcl-2, promoted apoptosis, and inhibited cell proliferation in OE 19 cells. Overexpression of UHRF1 significantly blocked gAD-induced decrease of cell proliferation and increase of apoptosis in leptin-treated cells. Silence of adiponectin receptor 1/2 (AdipoR1/2) could inhibit gAD-induced decrease of cell proliferation and increase of apoptosis in leptin-treated cells. Silence of AdipoR2, but not AdipoR1, suppressed gAD-induced decrease of UHRF1 expression in leptin-treated cells. The results indicated that gAD inhibited the prooncogenic effects of leptin via AdipoR2-mediated suppression of UHRF1. Our study provides novel insights into the role of UHRF1 in the development of EAC and the mechanism of antitumor effect of gAD.
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xi Wu Road, Xi'an, 710004, Shaanxi, China.|Department of Gastroenterology, Xi'an Hospital of Traditional Chinese Medicine, No. 69, Feng Eighth Road, Xi'an, 710021, Shaanxi, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xi Wu Road, Xi'an, 710004, Shaanxi, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xi Wu Road, Xi'an, 710004, Shaanxi, China.
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xi Wu Road, Xi'an, 710004, Shaanxi, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xi Wu Road, Xi'an, 710004, Shaanxi, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xi Wu Road, Xi'an, 710004, Shaanxi, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xi Wu Road, Xi'an, 710004, Shaanxi, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Di
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xi Wu Road, Xi'an, 710004, Shaanxi, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Xi'an Hospital of Traditional Chinese Medicine, No. 69, Feng Eighth Road, Xi'an, 710021, Shaanxi, China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xi Wu Road, Xi'an, 710004, Shaanxi, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xi Wu Road, Xi'an, 710004, Shaanxi, China. ZJzhangjun8805@tom.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D052242:Adiponectin / Q000378:metabolism*; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D054419:Receptors, Adiponectin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
chemical_list: C499918:ADIPOQ protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D022762:CCAAT-Enhancer-Binding Proteins; D020738:Leptin; D009363:Neoplasm Proteins; D054419:Receptors, Adiponectin; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Adiponectin; Adiponectin receptor; Esophageal adenocarcinoma; Leptin; Ubiquitin-like with PHD and ring finger domains 1