MiR-21/RASA1 axis affects malignancy of colon cancer cells via RAS pathways
MiR-21/RASA1 axis affects malignancy of colon cancer cells via RAS pathways作者机构:Department of GastroenterologyGuangdong General HospitalGuangdong Academy of Medical Sciences Department of Gastroenterologythe Third People’s Hospital of Huizhou Graduate SchoolSouthern Medical University Research Center of Medical SciencesGuangdong General HospitalGuangdong Academy of Medical Sciences Department of Gastroenterologythe Third Affiliated Hospital of Sun Yat-sen University Department of PathologyGuangdong General HospitalGuangdong Academy of Medical Sciences
出 版 物:《World Journal of Gastroenterology》 (世界胃肠病学杂志(英文版))
年 卷 期:2015年第21卷第5期
页 面:1488-1497页
核心收录:
学科分类:1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金:Supported by National Natural Science Foundation of China,No.81272770 Grants from Guangdong Natural Science Foundation,No.S2013020012746 Foundation of Guangdong Provincial Department of Science and Technology,No.2012A030400018
主 题:Colon cancer miR-21 RAS RASA1 RAS signaling pathwa
摘 要:AIM:To determine how the oncogene mi R-21 regulates the RAS signaling pathways and affects colon cancer cell ***:RAS p21 GTPase activating protein 1(RASA1) protein expression in six colon cancer cell lines was assessed by Western *** cancer RKO cells were chosen for transfection because they are KRAS wild type colon cancer cells whose RASA1 expression is significantly *** cells were transfected with vectors overexpressing or downregulating either mi R-21 or ***,a luciferase reporter assay was used to determine whether RASA1 is a gene target of mi ***,changes in m RNA and protein levels of RASA1,RASGTP,and other components of the RAS signaling pathways were assessed in transfected RKO cells by real-time quantitative reverse transcription-polymerase chain reaction,Western blot and ***,cell proliferation,apoptosis,invasion,and tumorformation ability w ere assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye assay,flow cytometry,transwell assay,and animal experiment,***:RASA1 protein levels were significantly decreased in RKO cells compared with the other 5 colon cancer cell lines,and RASA1 was confirmed as a target gene of mi ***,RASA1 m RNA and protein levels in pre-mi R-21-LV(up-regulation of mi R-21) cells were lower than those in anti-mi R-21-LV(down-regulation of mi R-21) cells(P 0.05).In addition,pre-mi R-21-LV or si RASA1(down-regulation of RASA1) cells showed higher cell proliferation,reduced apoptosis,increased expression of RAS-GTP,p-AKT,Raf-1,KRAS,and p-ERK1/2,and higher invasion and tumor formation ability,compared with control,antimi R-21-LV or pc DNA3.1-RASA1(up-regulation of RASA1) cells(P 0.05).CONCLUSION:RASA1 is a target gene of mi R-21,which promotes malignant behaviors of RKO cells through regulation of RASA1 expression.