title: Gremlin1 promotes carcinogenesis of glioma in vitro.
abstract: As the most prevalent and lethal type of brain tumours, gliomas, especially malignant ones, are relatively resistant to conventional therapies. Gremlin 1 (GREM1) is a secreted glycoprotein that is implicated in the maintenance of cancer stem cells in tumour hierarchy. In the current study, the role of GREM1 in the carcinogenesis of glioma was studied using a knockdown approach. We first examined the expression level of GREM1 in the clinical samples, and then evaluated the effect of GREM1 knockdown on the viability and colony formation capacity of U87-MG cells. Moreover, the migration ability, invasiveness, cell cycle, and apoptosis of GREM1-silenced cells were assessed. Furthermore, the involvement of functional GREM1 in the epithelial-mesenchymal transition (EMT) process of glioma was investigated by detecting the expression levels of glioma-associated oncogene homologue 3 (GLI3) and EMT-related molecules. Our results demonstrated that knockdown of GREM1 reduced cell viability, suppressed migration and invasion, and inhibited GLI3 expression and the EMT process in U87-MG cells. Meanwhile, GREM1 silencing promoted apoptosis in U87-MG cells through the accumulation of Bax, cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase (PARP) as well as the downregulation of Bcl-2. In addition, GREM1 knockdown abolished transforming growth factor (TGF)-β1-mediated activation of the Smad pathway, which may underlie the mechanism of GREM1-regulated EMT. In conclusion, GREM1 plays an important role in the development of glioma, and it may serve as a potential target in glioma therapy.
authors.affiliation: Department of Neurosurgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Yongchang
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Cunyi
authors.initials: C
authors.lastname: Zou
authors.affiliation: Department of Neurosurgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Tingzhong
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Cao
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000037:antagonists & inhibitors; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors
chemical_list: C486399:GREM1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1
keywords: Gremlin 1; Smad; TGF-β1; epithelial-mesenchymal transition; glioma; glioma-associated oncogene homologue 3