Zhang Xuemei, Ai Feiyan, Li Xiayu, Tian Li, Wang Xiaoyan, Shen Shourong, Liu Fen
Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan 410008, P.R. China.
Oncol Lett. 2017 Aug;14(2):2325-2333. doi: 10.3892/ol.2017.6444. Epub 2017 Jun 21.
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. 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.
微小RNA（miRNA/miR）表达失调与癌症的发生和发展存在因果关系。然而，失调的miRNA诱导结直肠癌发生的确切机制仍不清楚。在本研究中，在结直肠癌细胞系和临床标本中发现了miR-34a的下调。临床研究表明，miR-34a表达与远处转移呈负相关，与人结直肠癌标本的分化和生存呈正相关。miRNA功能分析表明，miR-34a在SW480细胞中与Notch1和Jagged1的假定3'-非翻译区结合，从而减弱结肠癌细胞的迁移和侵袭。此外，还发现miR-34a通过Notch1和Jagged1下调波形蛋白和纤连蛋白的表达。总体而言，这些数据表明miR-34a通过靶向和调节Notch信号通路在抑制结直肠癌转移中起关键作用。
