MicroRNA-34a suppresses colorectal cancer metastasis by regulating Notch signaling

被引:71
作者
Zhang, Xuemei [1 ,2 ,3 ]
Ai, Feiyan [1 ,2 ]
Li, Xiayu [1 ,2 ]
Tian, Li [1 ,2 ]
Wang, Xiaoyan [1 ,2 ]
Shen, Shourong [1 ,2 ]
Liu, Fen [1 ,2 ]
机构
[1] Cent South Univ, Xiangya Hosp 3, Dept Gastroenterol, 138 Tong Zi Po Rd, Changsha 410013, Hunan, Peoples R China
[2] Hunan Key Lab Nonresolving Inflammat & Canc, Changsha 410008, Hunan, Peoples R China
[3] Cent South Univ, Canc Res Inst, Changsha 410013, Hunan, Peoples R China
基金
中国国家自然科学基金;
关键词
microRNAs; colorectal cancer; Notch1; Jagged1; cell metastasis; TUMOR-SUPPRESSOR; GENE-EXPRESSION; MIR-34; FAMILY; INVASION; P53; STATISTICS; ACTIVATION; APOPTOSIS; PATHWAY; GROWTH;
D O I
10.3892/ol.2017.6444
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Dysregulation of microRNA (miRNA/miR) expression is causally associated with cancer initiation and progression. However, the precise mechanisms by which dysregulated miRNAs induce colorectal tumorigenesis remain unknown. In the present study, downregulation of miR-34a was identified in colorectal cancer cell lines and clinical specimens. Clinical studies revealed that miR-34a expression was negatively associated with distant metastasis, and positively associated with differentiation and survival of human colorectal cancer specimens. In vitro miRNA functional assays demonstrated that miR-34a bound to the putative 3'-untranslated regions of Notch1 and Jagged1 in SW480 cells, and thereby attenuated the migration and invasion of the colon cancer cells. It was additionally identified that miR-34a downregulated the expression of vimentin and fibronectin via Notch1 and Jagged1. Overall, these data indicate that miR-34a serves a key role in suppressing colorectal cancer metastasis by targeting and regulating Notch signaling.
引用
收藏
页码:2325 / 2333
页数:9
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