title: Feedback Loop Regulation of SCAP/SREBP-1 by miR-29 Modulates EGFR Signaling-Driven Glioblastoma Growth.
abstract: Dysregulated lipid metabolism is a characteristic of malignancies. Sterol regulatory element binding protein 1 (SREBP-1), a transcription factor playing a central role in lipid metabolism, is highly activated in malignancies. Here, we unraveled a link between miR-29 and the SCAP (SREBP cleavage-activating protein)/SREBP-1 pathway in glioblastoma (GBM) growth. Epidermal growth factor receptor (EGFR) signaling enhances miR-29 expression in GBM cells via upregulation of SCAP/SREBP-1, and SREBP-1 activates miR-29 expression via binding to specific sites in its promoter. In turn, miR-29 inhibits SCAP and SREBP-1 expression by interacting with their 3' UTRs. miR-29 transfection suppressed lipid synthesis and GBM cell growth, which were rescued by the addition of fatty acids or N-terminal SREBP-1 expression. Xenograft studies showed that miR-29 mimics significantly inhibit GBM growth and prolong the survival of GBM-bearing mice. Our study reveals a previously unrecognized negative feedback loop in SCAP/SREBP-1 signaling mediated by miR-29 and suggests that miR-29 treatment may represent an effective means to target GBM.
authors.affiliation: Department of Radiation Oncology, James Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Ru
authors.affiliation: Department of Radiation Oncology, James Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Hu
authors.affiliation: Department of Radiation Oncology, James Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Geng
authors.affiliation: Center for Biostatistics, Department of Bioinformatics, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Mo
authors.affiliation: Department of Radiation Oncology, James Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Chunming
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Neurosurgery, James Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Yoo
authors.affiliation: Department of Radiation Oncology, James Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Radiation Oncology, James Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, James Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, OH 43210, USA; Department of Neurosurgery, James Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Jeffrey Yunhua
authors.initials: JY
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakano
authors.affiliation: CarMeN Laboratory, INSERM U1060, INRA 1397, Faculté de Médecine Lyon Sud BP 12, Université de Lyon, 69921 Oullins Cedex, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Lefai
authors.affiliation: Department of Neurosurgery, James Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Balveen
authors.initials: B
authors.lastname: Kaur
authors.affiliation: Department of Radiation Oncology, James Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Arnab
authors.initials: A
authors.lastname: Chakravarti
authors.affiliation: Department of Radiation Oncology, James Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, OH 43210, USA. Electronic address: deliang.guo@osumc.edu.
authors.forename: Deliang
authors.initials: D
authors.lastname: Guo
mesh_terms: D000818:Animals; D066246:ErbB Receptors / Q000235:genetics*; D005246:Feedback; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*
chemical_list: C547014:MIRN29 microRNA, mouse; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; C497387:SREBF1 protein, human; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; C512478:EGFR protein, human; C541485:EGFR protein, mouse; D066246:ErbB Receptors
keywords: EGFR; SCAP; SREBP-1; glioblastoma; lipid metabolism; miR-29