c-MYC调节的miRNA-92b在结直肠癌发生发展中的功能及机制探究（英文）  

c-MYC-Regulated miRNA-92b Inhibits Expression of The E3 Ligase FBXW7 in Colorectal Cancer

作　　者：尹晓飞[1] 吴帅[1] 杨远勤[2] 方先龙 徐海能[1] 刘新垣[1,2] 郑树[3] 章康健[1,4] 

机构地区：[1]中国科学院上海生命科学研究院生物化学与细胞生物学研究所,细胞生物学重点实验室,上海200031 [2]浙江理工大学生命科学学院新元医学与生物技术研究所,杭州310018 [3]浙江大学医学院附属第二医院肿瘤研究所,教育部恶性肿瘤预警与干预重点实验室,浙江省医学分子生物学重点实验室,杭州310009 [4]四川辉阳生命工程股份有限公司,成都610021

出　　处：《生物化学与生物物理进展》2016年第7期673-683,共11页Progress In Biochemistry and Biophysics

基　　金：supported by grants from the Sichuan Science and Technology Project(2013ZZ0004);the Shanghai Institutes for Biological Science,Chinese Academy of Sciences&the Sichuan Huiyang Life Science and Technology Corp.Research Program(Y363S21763);National Basic Research Program of China(2011CB510104);a Zhejiang Sci-Tech University Grant(1204807-Y)

摘　　要：micro RNAs(miRNAs)在参与癌症发生、发展过程中起着十分重要的作用.目前,miR-92b在结直肠癌中的作用及相关机制还未见报道.本研究探讨了miR-92b在结直肠癌发生发展中的功能及潜在机制.采用RT-qPCR方法发现,miR-92b在人结直肠癌临床样本中与癌旁组织相比显著高表达.通过结肠癌细胞株SW620稳转细胞及裸鼠皮下成瘤模型,发现过表达miR-92b可以显著促进细胞增殖及体内肿瘤生长.同时还发现miR-92b可以分泌形式存在于胞外及外周血中,提示miR-92b是一个具有分泌特性的micro RNA.在分子机理方面,c-MYC可通过调节miR-92b的启动子活性从而促进后者转录,并且c-MYC在结直肠癌组织样本中也存在高表达.进一步,通过在线预测、报告质粒活性检测及蛋白质印迹技术证实FBXW7是一个新的miR-92b靶基因.由于FBXW7已报道为c-MYC泛素降解过程中的关键泛素化连接酶之一,本研究结果提示结直肠癌中c-MYC、miR-92b及FBXW7三者间可能存在分子调节环路.综上所述,本研究为miR-92b在结直肠癌中的功能及机制提供了新的视角,并为miR-92b在结直肠癌早期诊断中的应用提供了新的参考.Colorectal cancer（CRC） is the third leading cause of cancer-related death worldwide.Many micro RNAs（miRNAs） have been reported to be abnormally expressed in CRC.Recent studies have identified miR-92 b as a potential oncogene in several types of cancer.However,the role of miR-92 b in CRC has not been clarified.This study aimed to elucidate the role of miR-92 b in CRC progression.Relative quantitative PCR revealed that miR-92 b expression was significantly increased in human CRC tissues compared to the adjacent tissues.Overexpression of miR-92 b in the colorectal cancer cell line SW620 substantially increased cell viability in vitro and xenograft tumor growth in vivo.Also,mi R-92 b was identified as a secreted mi RNA,which can be detected in both cultured medium and the peripheral blood of xenograft mice.Furthermore,we demonstrated that c-MYC,which was also elevated in CRC tissues,promoted the transcription of mi R-92 b by regulating its promoter activity.Luciferase assay and Western blot analysis revealed that FBXW7 was a novel target of mi R-92 b and can be negatively regulated by c-MYC.As FBXW7 is a major E3 ligase of c-MYC,our data suggested a potential positive regulatory feedback loop among c-MYC,miR-92 b and FBXW7 in CRC.Collectively,we partly provided evidence on how miR-92 b is regulated and the potential implications of miR-92 b in CRC diagnosis.

关 键 词：miR-92b 结直肠癌 分泌型micro RNA C-MYC FBXW7 

分 类 号：Q28[生物学—细胞生物学]