miR-23a promotes invasion of glioblastoma via HOXD10-regulated glial-mesenchymal transition

查看全文 作　　者：Kazuhiro [1]Yachi;Masumi [1,2,3]Tsuda;Shinji [1,5]Kohsaka;Lei [1,2]Wang;Yoshitaka [1]Oda;Satoshi [1]Tanikawa;Yusuke [4]Ohba;Shinya [1,2,3]Tanaka

机构地区：[1]Department of Cancer Pathology,Faculty of Medicine,Hokkaido University,Sapporo,Japan;[2]Global Station for Soft Matter,Global Institution for Collaborative Research and Education,Hokkaido University,Sapporo,Japan;[3]Institute for Chemical Reaction Design and Discovery(WPI-ICReDD),Hokkaido University,Sapporo,Japan;[4]Department of Cell Physiology,Faculty of Medicine,Hokkaido University,Sapporo,Japan;[5]Present address:Division of Cellular Signaling,National Cancer Center Research Institute,Tokyo,Japan

出　　处：《Signal Transduction and Targeted Therapy》索引2018年第3卷第1期,共10页

基　　金：This work was supported,in part,by Grants-in-Aid from the Ministry of Education,Culture,Sports,Science,and Technology;Japanese Society for the Promotion of Science;Ministry of Health,Labor,and Welfare of Japan as well as a grant from the Japanese Science and Technology Agency;In addition,this research was supported by Global Station for Soft Matter,a project of Global Institution for Collaborative Research and Education at Hokkaido University.Institute for Chemical Reaction Design and Discovery(ICReDD)was established by World Premier International Research Initiative(WPI),MEXT,Japan. 摘　　要：Glioblastoma is the most aggressive and invasive brain tumor and has a poor prognosis;elucidating the underlying molecular mechanisms is essential to select molecular targeted therapies.Here,we investigated the effect of microRNAs on the marked invasiveness of glioblastoma.U373 glioblastoma cells were infected with 140 different microRNAs from an OncomiR library,and the effects of the invasion-related microRNAs and targeted molecules were investigated after repeated Matrigel invasion assays.Screening of the OncomiR library identified miR-23a as a key regulator of glioblastoma invasion.In six glioblastoma cell lines,a positive correlation was detected between the expression levels of miR-23a and invasiveness.A luciferase reporter assay demonstrated that homeobox D10(HOXD10)was a miR-23a-target molecule,which was verified by high scores from both the PicTar and miRanda algorithms.Forced expression of miR-23a induced expression of invasion-related molecules,including uPAR,RhoA,and RhoC,and altered expression of glial-mesenchymal transition markers such as Snail,Slug,MMP2,MMP9,MMP14,and E-cadherin;however,these changes in expression levels were reversed by HOXD10 overexpression.Thus,miR-23a significantly promoted invasion of glioblastoma cells with polarized formation of focal adhesions,while exogenous HOXD10 overexpression reversed these phenomena.Here,we identify miR-23a-regulated HOXD10 as a pivotal regulator of invasion in glioblastoma,providing a novel mechanism for the aggressive invasiveness of this tumor and providing insight into potential therapeutic targets. 关键词：HOXD10 INVASION MIR

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miR-23a promotes invasion of glioblastoma via HOXD10-regulated glial-mesenchymal transition

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