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FtMt promotes glioma tumorigenesis and angiogenesis via lncRNA SNHG1/miR-9-5p axis
Affiliation:1. Department of Hematology, The Affiliated Hospital of Gulin Medical University, Guilin, China;2. Department of Ultrasonic Medicine, The Affiliated First Hospital of Harbin Medical University, Harbin, China;3. Department of Digestive Internal Medicine & Photodynamic Therapy Center, Harbin Medical University Cancer Hospital, Harbin, China;1. Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany;2. Institute of Pharmacology and Toxicology, Medical Faculty, RWTH-Aachen University, Aachen, Germany;3. Department of Pathology, University Hospital of Cologne, Cologne, Germany;4. Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), University Hospital RWTH-Aachen, Aachen, Germany;1. Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;2. Department of Gynaecology and Obstetrics, Fudan University, Shanghai, China;3. Department of Gynaecology, Huangpu Branch of the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;4. Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;5. Faculty of Life Science, Sun Yat-sen University, Guangzhou, China;1. The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079, PR China;2. Department of Endodontics, School & Hospital of Stomatology, Wuhan University, Wuhan, PR China
Abstract:ObjectiveThis study is to investigate the effects and the mechanisms of mitochondrial ferritin (FtMt) on the glioma tumorigenesis and angiogenesis.MethodsFtMt expression was detected in glioma tissues and cells as well as in nude mouse tissues. Cell proliferation and apoptosis rate were observed following transfection of LV-FtMt or sh-FtMt in glioma cell line. Moreover, glioma cells with FtMt over-expression/knockdown were co-cultured with human umbilical vein endothelial cells (HUVECs) to observe its function on HUVEC proliferation, angiogenic ability and the vascular endothelial growth factor (VEGF) content. Gain and loss of function of small nucleolar RNA host gene 1 (SNHG1) and miR-9-5p were performed in glioma cells and GBM nude mice to observe its effect on glioma cell proliferation and HUVEC angiogenic ability. Luciferase reporter gene and RIP assay were employed to inspect the interactions among SNHG1, FtMt and miR-9-5p. Additionally, a xenograft mouse model was applied to determine the role of FtMt in glioma.ResultsIn this work, FtMt was strongly expressed in glioma tissues and cells as well as in nude mouse tumor tissues. The employment of the loss-of and gain-of functions assays illustrated that FtMt enhanced glioma tumorigenesis and angiogenesis. Mechanistically, our findings showed that FtMt positively related to SNHG1 while negatively correlated with miR-9-5p, and both SNHG1 and FtMt can competitively bind with miR-9-5p. Besides, the inhibition effects of sh-FtMt on glioma were surveyed in vivo experiments.ConclusionEvidence in this study suggested that FtMt promotes glioma tumorigenesis and angiogenesis via SNHG1 mediated miR-9-5p expression, which may provide a theoretical basis for glioma treatment.
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