标题：microRNA-335 inhibits colorectal cancer HCT116 cells growth and epithelial-mesenchymal transition (EMT) process by targeting Twist1
作者：Wang, Jingyuan; Wang, Xuemei; Liu, Fengjun; Fu, Yuguang
作者机构：[Wang, Jingyuan; Liu, Fengjun] Shandong Univ, Qilu Hosp, Dept Gen Surg, Jinan, Shandong, Peoples R China.; [Wang, Jingyuan] Jining 1 Peoples Hosp, D 更多
通讯作者地址：[Fu, YG]Shandong Inst Parasit Dis, Dept Gen Surg, 11 Taibai Middle Rd, Jining 272033, Peoples R China.
摘要：Colorectal cancer is one of the most commonly diagnosed cancers. Recently, several microRNAs (miRNAs) have been characterized as oncogenes or tumor suppressors in colorectal cancer. This study was aimed to explore the tumor suppressive effects and its underling mechanism of miR-335 on colorectal cancer cells. Human colorectal cancer HCT116 cells were employed and the expression of miR-335 in cells was altered by transfection with miR-335 mimic and miR-335 inhibitor. Thereafter, CCK-8 assay, flow cytometry, Transwell assay and Western blotting were used to detect cell viability, apoptosis, migration, invasion, and the expression of epithelial-mesenchymal transition (EMT)-related proteins. Dual luciferase activity assay was performed to test whether Twist1 was a direct target of miR-335. Moreover, cells were co-transfected with miR-335 inhibitor and Twist1 siRNA, and then cell growth and metastasis were re-evaluated. miR-335 overexpression inhibited cell viability, migration and invasion, and promoted apoptotic cells rate. miR-335 overexpression up-regulated E-Cadherin, while down-regulated N-Cadherin, Vimentin and Snail. Twist1 was a direct target of miR-335, and Twist1 silence promoted apoptosis, and abolished miR-335 suppression induced increases in cell viability, migration, invasion, and abnormal expressions of EMT-related proteins. Besides, Twist1 silence abolished miR-335 suppression induced activations of p65 and l kappa B alpha, and miR-335 suppression induced up-regulations of Wnt3a, Wnt5a and p-Catenin. miR-335 inhibited HCT116 cells growth, migration, invasion, and ETM process. miR-335 exhibited tumor suppressive effects possibly by inhibition of Twsit1 and thus inactivating NF-kappa B and Wnt/beta-catenin pathways.