Xiao Yue1, Dechen Cao2, FengMing Lan2, Qiang Pan2, Tingyi Xia2, Huiming Yu2. 1. 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. 2. 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.).
Abstract
BACKGROUND: 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. METHODS: Biochemical, luciferase reporter, and hromatin immunoprecipitation PCR assays characterized the function and regulatory mechanisms of miR-301a in glioma invasion. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND:miR-301a is frequently dysregulated and specific to humantumors, 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. METHODS: Biochemical, luciferase reporter, and hromatin immunoprecipitation PCR assays characterized the function and regulatory mechanisms of miR-301a in glioma invasion. RESULTS: 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 gliomapatients. 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. CONCLUSIONS: 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: Markus Hutterer; Elke Hattingen; Christoph Palm; Martin Andreas Proescholdt; Peter Hau Journal: Neuro Oncol Date: 2014-12-27 Impact factor: 12.300
Authors: Allison K Simi; Alişya A Anlaş; Melody Stallings-Mann; Sherry Zhang; Tiffaney Hsia; Magdalena Cichon; Derek C Radisky; Celeste M Nelson Journal: Cancer Res Date: 2018-02-26 Impact factor: 12.701
Authors: Alyson A Fiorillo; Christopher B Tully; Jesse M Damsker; Kanneboyina Nagaraju; Eric P Hoffman; Christopher R Heier Journal: Physiol Genomics Date: 2018-06-08 Impact factor: 3.107