MicroRNA-451 suppresses tumor cell growth by down-regulating IL6R gene expression.
The miR-451 was found to be frequently down-regulated in tumors, indicating that miR-451 could play an important role in carcinogenesis. This study uncovered the mechanism by which the miR-451 functions as a tumor suppressor. The target genes of miR-451 were determined using target gene prediction softwares. Then the miR-451 mimics were introduced into RKO and Hela cells respectively. The proliferation and invasion of cells were monitored by MTT, cell cycle and in vitro extracellular matrix invasion assays. Also the angiogenesis of HUVEC cells transfected with miR-451 mimics was examined. Subsequently, IL6R, a predicted target gene of miR-451, was studied by real time PCR, Western blotting, and siRNA technologies. The mRNA and protein levels of IL6R gene were found to be down-regulated in the RKO and Hela cells transfected with miR-451 mimics. Consequently, the cell proliferation was inhibited. Also, the invasion of RKO cells was suppressed. Furthermore, the angiogenesis of HUVEC cells transfected with miR-451 mimics was assayed and the decreased angiogenic ability was detected compared to the controls. All these results were validated by IL6R siRNA experiments. The IL6R gene is a target gene of miR-451. The miR-451 behaves as a tumor suppressor, probably by targeting the IL6R pathway.
Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Dong
D
Liu
Department of Medical Genetics, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Cong
C
Liu
Department of Medical Genetics, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Xiyin
X
Wang
Institute for Experimental Pathology and Faculty of Medicine, University of Iceland, Keldur, Reykjavik, Iceland.
Sigurdur
S
Ingvarsson
Department of Medical Genetics, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address: huiping@mail.hust.edu.cn.
Huiping
H
Chen
D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D018919:Neovascularization, Physiologic / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019947:Receptors, Interleukin-6 / Q000235:genetics*; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
C531201:MIRN451 microRNA, human; D035683:MicroRNAs; D019947:Receptors, Interleukin-6
Down-regulating; IL6R; Tumor suppressor; miR-451