title: MiR-301a is activated by the Wnt/β-catenin pathway and promotes glioma cell invasion by suppressing SEPT7.
abstract: miR-301a is frequently dysregulated and specific to human tumors, playing a critical role in tumorigenesis; however, the exact functions and regulatory mechanisms of miR-301a in glioma cells remain largely unknown. Herein, we show that miR-301a activated by the Wnt/β-catenin pathway promoted the invasion of glioma cells by directly targeting SEPT7.
  
  
  
  Biochemical, luciferase reporter, and hromatin immunoprecipitation PCR assays characterized the function and regulatory mechanisms of miR-301a in glioma invasion.
  
  
  
  Initially, we detected the expression of miR-301a in glioma tissues and identified that miR-301a had increased, with ascending grades of the tumor. Furthermore, high levels of miR-301a were associated with a poorer prognosis in glioma patients. It is important to note that the Wnt/β-catenin/TCF4 pathway enhanced miR-301a expression by binding to the promoter region. To determine the oncogenic functions of miR-301a in glioma, SEPT7 was supported as the direct target gene. In addition, the Wnt/β-catenin pathway repressed SEPT7 expression, which was dependent on miR-301a in glioma cells. Finally, miR-301a was activated by Wnt/β-catenin and then promoted invasion of glioma cells by inhibiting the expression of SEPT7 in vitro and in vivo.
  
  
  
  Our findings revealed the mechanism of action for miR-301a in tumor cell invasion. Moreover, the Wnt/miR-301a/SEPT7 signaling axis might be a novel target in treating glioma.
authors.affiliation: Tianjin Huanhu Hospital, Tianjin Neurosurgery Institute, Tianjin , China (X.Y., D.C.); Department of Radiation Oncology, Tianjin Hospital, Tianjin , China (F.L.); Department of Neurosurgery, Laiwu City People's Hospital, Laiwu, China (Q.P.); Department of Radiation Oncology, P.L.A Airforce General Hospital, Beijing, China (T.X.); Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiotherapy, Peking University Cancer Hospital & Institute, Beijing, China (H.Y.) yuexiaolfm@163.com dreamlfm1986@163.com.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yue
authors.affiliation: Tianjin Huanhu Hospital, Tianjin Neurosurgery Institute, Tianjin , China (X.Y., D.C.); Department of Radiation Oncology, Tianjin Hospital, Tianjin , China (F.L.); Department of Neurosurgery, Laiwu City People's Hospital, Laiwu, China (Q.P.); Department of Radiation Oncology, P.L.A Airforce General Hospital, Beijing, China (T.X.); Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiotherapy, Peking University Cancer Hospital & Institute, Beijing, China (H.Y.).
authors.forename: Dechen
authors.initials: D
authors.lastname: Cao
authors.affiliation: Tianjin Huanhu Hospital, Tianjin Neurosurgery Institute, Tianjin , China (X.Y., D.C.); Department of Radiation Oncology, Tianjin Hospital, Tianjin , China (F.L.); Department of Neurosurgery, Laiwu City People's Hospital, Laiwu, China (Q.P.); Department of Radiation Oncology, P.L.A Airforce General Hospital, Beijing, China (T.X.); Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiotherapy, Peking University Cancer Hospital & Institute, Beijing, China (H.Y.).
authors.forename: FengMing
authors.initials: F
authors.lastname: Lan
authors.affiliation: Tianjin Huanhu Hospital, Tianjin Neurosurgery Institute, Tianjin , China (X.Y., D.C.); Department of Radiation Oncology, Tianjin Hospital, Tianjin , China (F.L.); Department of Neurosurgery, Laiwu City People's Hospital, Laiwu, China (Q.P.); Department of Radiation Oncology, P.L.A Airforce General Hospital, Beijing, China (T.X.); Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiotherapy, Peking University Cancer Hospital & Institute, Beijing, China (H.Y.).
authors.forename: Qiang
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Tianjin Huanhu Hospital, Tianjin Neurosurgery Institute, Tianjin , China (X.Y., D.C.); Department of Radiation Oncology, Tianjin Hospital, Tianjin , China (F.L.); Department of Neurosurgery, Laiwu City People's Hospital, Laiwu, China (Q.P.); Department of Radiation Oncology, P.L.A Airforce General Hospital, Beijing, China (T.X.); Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiotherapy, Peking University Cancer Hospital & Institute, Beijing, China (H.Y.).
authors.forename: Tingyi
authors.initials: T
authors.lastname: Xia
authors.affiliation: Tianjin Huanhu Hospital, Tianjin Neurosurgery Institute, Tianjin , China (X.Y., D.C.); Department of Radiation Oncology, Tianjin Hospital, Tianjin , China (F.L.); Department of Neurosurgery, Laiwu City People's Hospital, Laiwu, China (Q.P.); Department of Radiation Oncology, P.L.A Airforce General Hospital, Beijing, China (T.X.); Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiotherapy, Peking University Cancer Hospital & Institute, Beijing, China (H.Y.).
authors.forename: Huiming
authors.initials: H
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D058112:Septins / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D051153:Wnt Proteins; D051176:beta Catenin; C113158:SEPTIN7 protein, human; D058112:Septins
keywords: SEPT7; Wnt/β-catenin signaling; glioma; invasion; miR-301a