机构：[1]Department of Pathology, Nanfang Hospital,[2]Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, GuangdongProvince, People’s Republic of China[3]Prenatal Diagnosis Center & Genetic Disease Diagnosis and Treatment Center, Guangdong Women and Children Hospital,Guangzhou, Guangdong Province, People’s Republic of China[4]Department of Pathology, Shenzhen University, Shenzhen, People’s Republic of China深圳市康宁医院深圳医学信息中心[5]Institute ofPathology and Southern Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, People’s Republic of China[6]Department of Oncology,Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China临床科室肿瘤内科河北医科大学第四医院[7]Department of Pathology, People’s Hospital of ZhengzhouUniversity, Zhengzhou, Henan Province, People’s Republic of China
BACKGROUND & AIMS: Formin-like (FMNL) 2 is up-regulated in colorectal tumors and has been associated with tumor progression, but little is known about regulatory mechanisms. We investigated whether microRNAs regulate levels of FMNL2 in colorectal cancer (CRC) cells. METHODS: We used real-time polymerase chain reaction and immunoblot analyses to measure levels of miR-137, high-mobility group AT-hook (HMGA)1, and FMNL2 in CRC cells and tissue samples from patients (n = 50). We used luciferase reporter assays to determine the association between miR-137 and the FMNL2 3' untranslated region, and HMGA1 and the miR-137 promoter. Chromatin immunoprecipitation assays were used to assess direct binding of HMGA1 to the miR-137 promoter. RESULTS: miR-137 and miR-142-3p were predicted to bind FMNL2 based on bioinformatic data. Only the level of miR-137 had a significant inverse correlation with the level of FMNL2 protein in CRC cell lines and tissues. FMNL2 messenger RNA was targeted by miR-137; expression of miR-137 inhibited proliferation and invasion by CRC cells in vitro, and metastasis to liver and intestine by CRC xenografts in nude mice. HMGA1 bound to the promoter of miR-137 and activated its transcription, which reduced levels of FMNL2 in CRC cells. Ectopic expression of miR-137 in CRC cells inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and Akt, which reduced levels of matrix metalloproteinase 2, matrix metalloproteinase 9, and vascular endothelial growth factor; it also reduced invasiveness of CRC cells, inhibiting signaling via phosphatidylinositol-4,5-bisphosphate 3-kinase, Akt, and MAPK. CONCLUSIONS: Levels of miR-137 and HMGA1 are reduced, and levels of FMNL2 are increased, in CRC samples compared with adjacent normal mucosa. In CRC cells, miR-137 targets FMNL2 messenger RNA and is regulated by the transcription factor HMGA1. Expression of miR-137 reduces CRC cell invasion in vitro and metastasis of tumor xenografts in mice. FMNL2 appears to activate phosphatidylinositol-4,5-bisphosphate 3-kinase, protein kinase B (Akt), and MAPK signaling pathways.
基金：
Supported by National Natural Science Foundation of China
(81272759, 81172382, 81071735); Major projects of National
Natural Science Foundation of China (81090422); National Basic
Research Program of China (973 Program, 2010CB529402,
2010CB529403); the key NSFC-Guangdong Joint Project of China
(U1201226); the Science and Technology Planning Project of
Guangdong Province (2010B031500012); the Key Scientific and
Technical Innovation Project of Higher Education of Guangdong
Province (GXZD1016); Natural Science Foundation of Guangdong
Province (S2012010009669); Research Fund for Subject and
Profession development of Higher Education of Guangdong
Province (2012KJCX0026); Research Fund for the Science and
technology Star of Zhujiang of Guangzhou City (2011J2200074).
第一作者机构：[1]Department of Pathology, Nanfang Hospital,[2]Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, GuangdongProvince, People’s Republic of China[*1]Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Repulic of China.
通讯作者：
通讯机构：[1]Department of Pathology, Nanfang Hospital,[2]Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, GuangdongProvince, People’s Republic of China[*1]Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Repulic of China.
推荐引用方式(GB/T 7714)：
LI LIANG,XIANZHENG LI,XIAOJING ZHANG,et al.MicroRNA-137, an HMGA1 Target, Suppresses Colorectal Cancer Cell Invasion and Metastasis in Mice by Directly Targeting FMNL2[J].GASTROENTEROLOGY.2013,144(3):624-+.doi:10.1053/j.gastro.2012.11.033.
APA：
LI LIANG,XIANZHENG LI,XIAOJING ZHANG,ZHENBING LV,GUOYANG HE...&YANQING DING.(2013).MicroRNA-137, an HMGA1 Target, Suppresses Colorectal Cancer Cell Invasion and Metastasis in Mice by Directly Targeting FMNL2.GASTROENTEROLOGY,144,(3)
MLA：
LI LIANG,et al."MicroRNA-137, an HMGA1 Target, Suppresses Colorectal Cancer Cell Invasion and Metastasis in Mice by Directly Targeting FMNL2".GASTROENTEROLOGY 144..3(2013):624-+
医学