Downregulation of Notch-regulated Ankyrin Repeat Protein Exerts Antitumor Activities against Growth of Thyroid Cancer
Downregulation of Notch-regulated Ankyrin Repeat Protein Exerts Antitumor Activities against Growth of Thyroid Cancer作者机构：Graduate School Shanghai Second Military Medical University Shanghai 200433 China Department of General Surgery Xinhua Hospita/Affiliated to Shanghai Jiao Tong Univeisity School of Medicine Shanghai 200092 China Clinical College Yancheng Institute of Health Sciences Yancheng Jiangsu 224000 China Department of First General Surgery Changhai Hospital Second Military Medical University Shanghai 200433 China
出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)
年 卷 期：2016年第129卷第13期
页 面：1544-1552页
核心收录：
学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 071010[理学-生物化学与分子生物学] 1002[医学-临床医学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 10[医学]
基 金：supported by a technical fund of Shanghai Jiao Tong University School of Medicine the Key Program of Shanghai Municipal Commission of Health and Family Planning
主 题：Apoptosis Cell Cycle Checkpoints Notch-regulated Ankyrin Repeat Protein Thyroid Neoplasms
摘 要：Background： The Notch-regulated ankyrin repeat protein （NRARP） is recently found to promote proliferation of breast cancer cells. The role of NRARP in carcinogenesis deserves extensive investigations. This study attempted to investigate the expression of NRARP in thyroid cancer tissues and assess the influence of NRARP on cell proliferation, apoptosis, cell cycle, and invasion in thyroid cancer. Methods： Thirty-four cases with thyroid cancer were collected from the Department of General Surgery, Xinhua Hospital, Shanghai ]iao Tong University School of Medicine between 2011 and 2012. lmmunohistochemistry was used to detect the level of N RARP in cancer tissues. Lentivirus carrying NRARP-shRNA （Lenti-NRARP-shRNA） was applied to down-regulate NRARP expression. Cell viability was tested after treatment with Lenti-NRARP-shRNA using 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide assay. Apoptosis and cell cycle distribution were determined by flow cytometry. Cell invasion was tested using Transwell invasion assay. In addition, expressions of several cell cycle-associated and apoptosis-associated proteins were examined using Western blotting after transfection. Student＇s t-test, one-way analysis of variance （ANOVA）, or Kaplan Meier were used to analyze the differences between two group or three groups. Results： N RARP was highly expressed in thyroid cancer tissues. Lenti-NRARP-shRNA showed significantly inhibitory activities against cell growth at a multiplicity of infection of l 0 or higher （P 〈 0.05）. Lenti-NRARP-shRNA-induced G 1 arrest （BHTl 01 ： 72.57% ± 5.32%; g305C： 75.45% ± 5.26%） by promoting p21 expression, induced apoptosis by promoting bax expression and suppressing bcl-2 expression, and inhibited cell invasion by suppressing matrix metalloproteinase-9 expression. Conclusion： Downregulation of NRARP expression exerts significant antitumor activities against cell growth and invasion of thyroid cancer, that suggests a potential role of NRARP in thyro
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