Tuo Wang1, Ping Mao1, Yong Feng2, Bo Cui3, Bin Zhang4, Chen Chen5, Mingjie Xu6, Ke Gao1. 1. Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shannxi, China. 2. Department of Neurosurgery, The Hancheng People's Hospital, Weinan, Shannxi, China. 3. Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shannxi, China. 4. Department of Neurosurgery, Bao Ji Affiliated Hospital of Xi'an Medical University, Baoji, Shannxi, China. 5. Department of Neurosurgery, Mianxian Hospital, Mianxian, Shannxi, China. 6. Department of Neurosurgery, Traditional Chinese Medicine Hospital of Xixiang, Hanzhong, Shannxi, China.
Abstract
BACKGROUND: hsa_circ_0006168 is an oncogenic circular RNA in esophageal cancer. However, its role remains unclarified in tumor progression of gliomas, especially in glioblastoma (GBM). METHODS: Cell counting kit-8 assay, transwell assays, western blotting, and xenograft experiment, as well as colony formation assay and flow cytometry were performed to measure cell proliferation and motility. Expression of hsa_circ_0006168, microRNA (miR)-628-3p, insulin‑like growth factor 1 receptor (IGF1R), and Ras/extracellular signal regulated kinases (Erk)-related proteins were determined by quantitative real-time polymerase chain reaction and western blotting. The physical interaction was confirmed by dual-luciferase reporter assay and RNA pull-down assay. RESULTS: hsa_circ_0006168 and IGF1R were upregulated, and miR-628-5p was downregulated in human GBM tissues and cells. Functionally, blocking hsa_circ_0006168 and overexpressing miR-628-5p suppressed cell proliferation, migration, invasion, and expression of Vimentin and Snail (mesenchymal markers) in A172 and LN229 cells, accompanied with increased E-cadherin (epithelial marker), decreased colony formation, and promoted apoptosis rate. Silencing miR-628-5p counteracted the suppression of hsa_circ_0006168 deficiency on these behaviors, and restoring IGF1R blocked miR-628-5p-mediated inhibition as well. More importantly, hsa_circ_0006168 knockdown could delay xenograft tumor growth in vivo and lower Ras and phosphorylated Erk1/2 expression in vitro and in vivo. Mechanically, hsa_circ_0006168 targeted and sponged miR-628-5p, and IFG1R was a novel target for miR-628-5p. Inhibiting miR-628-5p could abrogate in vitro role of hsa_circ_0006168 knockdown, and similarly IGF1R upregulation counteracted miR-628-5p role. CONCLUSION: Silencing hsa_circ_0006168 might suppress GBM proliferation and motility via serving as competitive endogenous RNA for miR-628-5p and regulating IGF1R/Ras/Erk pathway.
BACKGROUND: hsa_circ_0006168 is an oncogenic circular RNA in esophageal cancer. However, its role remains unclarified in tumor progression of gliomas, especially in glioblastoma (GBM). METHODS: Cell counting kit-8 assay, transwell assays, western blotting, and xenograft experiment, as well as colony formation assay and flow cytometry were performed to measure cell proliferation and motility. Expression of hsa_circ_0006168, microRNA (miR)-628-3p, insulin‑like growth factor 1 receptor (IGF1R), and Ras/extracellular signal regulated kinases (Erk)-related proteins were determined by quantitative real-time polymerase chain reaction and western blotting. The physical interaction was confirmed by dual-luciferase reporter assay and RNA pull-down assay. RESULTS: hsa_circ_0006168 and IGF1R were upregulated, and miR-628-5p was downregulated in human GBM tissues and cells. Functionally, blocking hsa_circ_0006168 and overexpressing miR-628-5p suppressed cell proliferation, migration, invasion, and expression of Vimentin and Snail (mesenchymal markers) in A172 and LN229 cells, accompanied with increased E-cadherin (epithelial marker), decreased colony formation, and promoted apoptosis rate. Silencing miR-628-5p counteracted the suppression of hsa_circ_0006168 deficiency on these behaviors, and restoring IGF1R blocked miR-628-5p-mediated inhibition as well. More importantly, hsa_circ_0006168 knockdown could delay xenograft tumor growth in vivo and lower Ras and phosphorylated Erk1/2 expression in vitro and in vivo. Mechanically, hsa_circ_0006168 targeted and sponged miR-628-5p, and IFG1R was a novel target for miR-628-5p. Inhibiting miR-628-5p could abrogate in vitro role of hsa_circ_0006168 knockdown, and similarly IGF1R upregulation counteracted miR-628-5p role. CONCLUSION: Silencing hsa_circ_0006168 might suppress GBM proliferation and motility via serving as competitive endogenous RNA for miR-628-5p and regulating IGF1R/Ras/Erk pathway.
Authors: Yuanying Gong; Yufang Ma; Maksim Sinyuk; Sudan Loganathan; Reid C Thompson; Jann N Sarkaria; Wenbiao Chen; Justin D Lathia; Bret C Mobley; Stephen W Clark; Jialiang Wang Journal: Neuro Oncol Date: 2015-07-01 Impact factor: 12.300
Authors: David N Louis; Hiroko Ohgaki; Otmar D Wiestler; Webster K Cavenee; Peter C Burger; Anne Jouvet; Bernd W Scheithauer; Paul Kleihues Journal: Acta Neuropathol Date: 2007-07-06 Impact factor: 17.088