title: Let-7g-5p inhibits epithelial-mesenchymal transition consistent with reduction of glioma stem cell phenotypes by targeting VSIG4 in glioblastoma.
abstract: Epithelial-mesenchymal transition (EMT) and stem-like glioma cells display hallmark therapeutic resistance. Understanding of the mechanisms underlying these properties will be vital for the development of effective therapies. In this study, we found that VSIG4 protein is upregulated in glioblastoma. Overexpressing VSIG4 induced EMT and significantly promoted invasion and migration in glioblastoma U-87MG cells. Moreover, we showed that its overexpression promoted formation of glioma stem cell phenotypes in U-87MG cells. P4HB, VAMP8 and Connexin 43 (CX43) can promote temozolomide (TMZ) resistance in human glioma cells. We showed that P4HB, VAMP8 and CX43 protein were upregulated by VSIG4 in U-87MG cells, implying its upregulation might be a cause for temozolomide resistance. We found that let-7g-5p can inhibit VSIG4 protein expression, but it cannot degrade VSIG4 mRNA in U-87MG cells. Contrary to VSIG4, we demonstrated that overexpressing let-7g-5p promoted mesenchymal-epithelial transition (MET) and significantly inhibited invasion and migration consistent with the reduction of glioblastoma stem cell phenotypes in U-87MG cells. Thus, we concluded that let-7g-5p inhibits epithelial-mesenchymal transition (EMT) consistent with reduction of glioma stem cell (GSC) phenotypes by targeting VSIG4 in glioblastoma.
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Taishan Medical University, Tai'an, Shandong 271000, P.R. China.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Taishan Medical University, Tai'an, Shandong 271000, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Taishan Medical University, Tai'an, Shandong 271000, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Taishan Medical University, Tai'an, Shandong 271000, P.R. China.
authors.forename: Ning-Ning
authors.initials: NN
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China.
authors.forename: Yun-Jie
authors.initials: YJ
authors.lastname: Xie
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000473:pathology; D011951:Receptors, Complement / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D035683:MicroRNAs; D011951:Receptors, Complement; C414427:VSIG4 protein, human; C487931:mirnlet7 microRNA, human