title: ROCK1, a novel target of miR-145, promotes glioma cell invasion.
abstract: Malignant glioma is the most common type of cancer in the central nervous system, with highly invasive characteristics. The Rho-associated protein kinase (ROCK1) has been found to act as key regulator of actin cytoskeleton reorganization, a process closely associated with cancer cell invasion. microRNA-145 (miRNA-145) has been recently shown to act as a suppressor in several types of tumor, including glioma. However, the exact regulatory mechanism by which miR-145 inhibits glioma still remains to be uncovered. In this study, we report that the miR-145 level was significantly reduced in glioma tissues and in the human glioma cell lines U87 and U251, as compared to matched adjacent and normal brain tissues. We then identified the ROCK1 gene as a novel target of miR-145. The expression of ROCK1 was markedly upregulated in glioma tissues, as well as in U87 and U251 cells. Moreover, miR-145 significantly inhibited ROCK1 protein expression in U87 cells. We further show that miR-145 transfection considerably reduced the invasive ability of U87 cells, and was accompanied by the downregulation of matrix metalloproteinase 2 and 9, an effect which could be attenuated by overexpression of ROCK1. In conclusion, the present study suggests that miR-145 can inhibit U87 glioma cell invasion, at least partially via downregulation of the RhoA/ROCK1 pathway. In conclusion, this is the first study to report that ROCK1, as a novel target of miR-145, acts as a positive regulator of glioma cell invasion. Therefore, ROCK1 may constitute a promising target for glioma treatment.
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wan
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Renjun
authors.initials: R
authors.lastname: Peng
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Zigui
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Jiang
mesh_terms: D020413:3' Untranslated Regions; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015870:Gene Expression; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D054460:rho-Associated Kinases / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases