title: Effect of miR-142-3p on the M2 macrophage and therapeutic efficacy against murine glioblastoma.
abstract: BACKGROUND
  The immune therapeutic potential of microRNAs (miRNAs) in the context of tumor-mediated immune suppression has not been previously described for monocyte-derived glioma-associated macrophages, which are the largest infiltrating immune cell population in glioblastomas and facilitate gliomagenesis.
  
  
  METHODS
  An miRNA microarray was used to compare expression profiles between human glioblastoma-infiltrating macrophages and matched peripheral monocytes. The effects of miR-142-3p on phenotype and function of proinflammatory M1 and immunosuppressive M2 macrophages were determined. The therapeutic effect of miR-142-3p was ascertained in immune-competent C57BL/6J mice harboring intracerebral GL261 gliomas and in genetically engineered Ntv-a mice bearing high-grade gliomas. Student t test was used to evaluate the differences between ex vivo datasets. Survival was analyzed with the log-rank test and tumor sizes with linear mixed models and F test. All statistical tests were two-sided.
  
  
  RESULTS
  miR-142-3p was the most downregulated miRNA (approximately 4.95-fold) in glioblastoma-infiltrating macrophages. M2 macrophages had lower miR-142-3p expression relative to M1 macrophages (P = .03). Overexpression of miR-142-3p in M2 macrophages induced selective modulation of transforming growth factor beta receptor 1, which led to subsequent preferential apoptosis in the M2 subset (P = .01). In vivo miR-142-3p administration resulted in glioma growth inhibition (P = .03, n = 5) and extended median survival (miR-142-3p-treated C57BL/6J mice vs scramble control: 31 days vs 23.5 days, P = .03, n = 10; miR-142-3p treated Ntv-a mice vs scramble control: 32 days vs 24 days, P = .03, n = 9), with an associated decrease in infiltrating macrophages (R (2) = .303).
  
  
  CONCLUSIONS
  These data indicate a unique role of miR-142-3p in glioma immunity by modulating M2 macrophages through the transforming growth factor beta signaling pathway.
authors: Affiliations of authors: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China (SX, X-GL), Department of Neurosurgery (SX, JW, FW, L-YK, X-YL, EN, KG, TD, YY, FFL, GR, ABH), Department of Biostatistics (WQ), Department of Pathology (GNF), and Department of Experimental Therapeutics (GAC), University of Texas M. D. Anderson Cancer Center, Houston, TX; Baylor College of Medicine, Houston, TX (NKY); Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX (VF).
authors: Shuo
authors: S
authors: Xu
authors: Affiliations of authors: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China (SX, X-GL), Department of Neurosurgery (SX, JW, FW, L-YK, X-YL, EN, KG, TD, YY, FFL, GR, ABH), Department of Biostatistics (WQ), Department of Pathology (GNF), and Department of Experimental Therapeutics (GAC), University of Texas M. D. Anderson Cancer Center, Houston, TX; Baylor College of Medicine, Houston, TX (NKY); Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX (VF).
authors: Jun
authors: J
authors: Wei
authors: Affiliations of authors: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China (SX, X-GL), Department of Neurosurgery (SX, JW, FW, L-YK, X-YL, EN, KG, TD, YY, FFL, GR, ABH), Department of Biostatistics (WQ), Department of Pathology (GNF), and Department of Experimental Therapeutics (GAC), University of Texas M. D. Anderson Cancer Center, Houston, TX; Baylor College of Medicine, Houston, TX (NKY); Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX (VF).
authors: Fei
authors: F
authors: Wang
authors: Affiliations of authors: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China (SX, X-GL), Department of Neurosurgery (SX, JW, FW, L-YK, X-YL, EN, KG, TD, YY, FFL, GR, ABH), Department of Biostatistics (WQ), Department of Pathology (GNF), and Department of Experimental Therapeutics (GAC), University of Texas M. D. Anderson Cancer Center, Houston, TX; Baylor College of Medicine, Houston, TX (NKY); Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX (VF).
authors: Ling-Yuan
authors: LY
authors: Kong
authors: Affiliations of authors: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China (SX, X-GL), Department of Neurosurgery (SX, JW, FW, L-YK, X-YL, EN, KG, TD, YY, FFL, GR, ABH), Department of Biostatistics (WQ), Department of Pathology (GNF), and Department of Experimental Therapeutics (GAC), University of Texas M. D. Anderson Cancer Center, Houston, TX; Baylor College of Medicine, Houston, TX (NKY); Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX (VF).
authors: Xiao-Yang
authors: XY
authors: Ling
authors: Affiliations of authors: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China (SX, X-GL), Department of Neurosurgery (SX, JW, FW, L-YK, X-YL, EN, KG, TD, YY, FFL, GR, ABH), Department of Biostatistics (WQ), Department of Pathology (GNF), and Department of Experimental Therapeutics (GAC), University of Texas M. D. Anderson Cancer Center, Houston, TX; Baylor College of Medicine, Houston, TX (NKY); Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX (VF).
authors: Edjah
authors: E
authors: Nduom
authors: Affiliations of authors: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China (SX, X-GL), Department of Neurosurgery (SX, JW, FW, L-YK, X-YL, EN, KG, TD, YY, FFL, GR, ABH), Department of Biostatistics (WQ), Department of Pathology (GNF), and Department of Experimental Therapeutics (GAC), University of Texas M. D. Anderson Cancer Center, Houston, TX; Baylor College of Medicine, Houston, TX (NKY); Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX (VF).
authors: Konrad
authors: K
authors: Gabrusiewicz
authors: Affiliations of authors: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China (SX, X-GL), Department of Neurosurgery (SX, JW, FW, L-YK, X-YL, EN, KG, TD, YY, FFL, GR, ABH), Department of Biostatistics (WQ), Department of Pathology (GNF), and Department of Experimental Therapeutics (GAC), University of Texas M. D. Anderson Cancer Center, Houston, TX; Baylor College of Medicine, Houston, TX (NKY); Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX (VF).
authors: Tiffany
authors: T
authors: Doucette
authors: Affiliations of authors: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China (SX, X-GL), Department of Neurosurgery (SX, JW, FW, L-YK, X-YL, EN, KG, TD, YY, FFL, GR, ABH), Department of Biostatistics (WQ), Department of Pathology (GNF), and Department of Experimental Therapeutics (GAC), University of Texas M. D. Anderson Cancer Center, Houston, TX; Baylor College of Medicine, Houston, TX (NKY); Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX (VF).
authors: Yuhui
authors: Y
authors: Yang
authors: Affiliations of authors: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China (SX, X-GL), Department of Neurosurgery (SX, JW, FW, L-YK, X-YL, EN, KG, TD, YY, FFL, GR, ABH), Department of Biostatistics (WQ), Department of Pathology (GNF), and Department of Experimental Therapeutics (GAC), University of Texas M. D. Anderson Cancer Center, Houston, TX; Baylor College of Medicine, Houston, TX (NKY); Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX (VF).
authors: Nasser K
authors: NK
authors: Yaghi
authors: Affiliations of authors: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China (SX, X-GL), Department of Neurosurgery (SX, JW, FW, L-YK, X-YL, EN, KG, TD, YY, FFL, GR, ABH), Department of Biostatistics (WQ), Department of Pathology (GNF), and Department of Experimental Therapeutics (GAC), University of Texas M. D. Anderson Cancer Center, Houston, TX; Baylor College of Medicine, Houston, TX (NKY); Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX (VF).
authors: Virginia
authors: V
authors: Fajt
authors: Affiliations of authors: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China (SX, X-GL), Department of Neurosurgery (SX, JW, FW, L-YK, X-YL, EN, KG, TD, YY, FFL, GR, ABH), Department of Biostatistics (WQ), Department of Pathology (GNF), and Department of Experimental Therapeutics (GAC), University of Texas M. D. Anderson Cancer Center, Houston, TX; Baylor College of Medicine, Houston, TX (NKY); Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX (VF).
authors: Jonathan M
authors: JM
authors: Levine
authors: Affiliations of authors: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China (SX, X-GL), Department of Neurosurgery (SX, JW, FW, L-YK, X-YL, EN, KG, TD, YY, FFL, GR, ABH), Department of Biostatistics (WQ), Department of Pathology (GNF), and Department of Experimental Therapeutics (GAC), University of Texas M. D. Anderson Cancer Center, Houston, TX; Baylor College of Medicine, Houston, TX (NKY); Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX (VF).
authors: Wei
authors: W
authors: Qiao
authors: Affiliations of authors: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China (SX, X-GL), Department of Neurosurgery (SX, JW, FW, L-YK, X-YL, EN, KG, TD, YY, FFL, GR, ABH), Department of Biostatistics (WQ), Department of Pathology (GNF), and Department of Experimental Therapeutics (GAC), University of Texas M. D. Anderson Cancer Center, Houston, TX; Baylor College of Medicine, Houston, TX (NKY); Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX (VF).
authors: Xin-Gang
authors: XG
authors: Li
authors: Affiliations of authors: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China (SX, X-GL), Department of Neurosurgery (SX, JW, FW, L-YK, X-YL, EN, KG, TD, YY, FFL, GR, ABH), Department of Biostatistics (WQ), Department of Pathology (GNF), and Department of Experimental Therapeutics (GAC), University of Texas M. D. Anderson Cancer Center, Houston, TX; Baylor College of Medicine, Houston, TX (NKY); Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX (VF).
authors: Frederick F
authors: FF
authors: Lang
authors: Affiliations of authors: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China (SX, X-GL), Department of Neurosurgery (SX, JW, FW, L-YK, X-YL, EN, KG, TD, YY, FFL, GR, ABH), Department of Biostatistics (WQ), Department of Pathology (GNF), and Department of Experimental Therapeutics (GAC), University of Texas M. D. Anderson Cancer Center, Houston, TX; Baylor College of Medicine, Houston, TX (NKY); Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX (VF).
authors: Ganesh
authors: G
authors: Rao
authors: Affiliations of authors: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China (SX, X-GL), Department of Neurosurgery (SX, JW, FW, L-YK, X-YL, EN, KG, TD, YY, FFL, GR, ABH), Department of Biostatistics (WQ), Department of Pathology (GNF), and Department of Experimental Therapeutics (GAC), University of Texas M. D. Anderson Cancer Center, Houston, TX; Baylor College of Medicine, Houston, TX (NKY); Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX (VF).
authors: Gregory N
authors: GN
authors: Fuller
authors: Affiliations of authors: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China (SX, X-GL), Department of Neurosurgery (SX, JW, FW, L-YK, X-YL, EN, KG, TD, YY, FFL, GR, ABH), Department of Biostatistics (WQ), Department of Pathology (GNF), and Department of Experimental Therapeutics (GAC), University of Texas M. D. Anderson Cancer Center, Houston, TX; Baylor College of Medicine, Houston, TX (NKY); Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX (VF).
authors: George A
authors: GA
authors: Calin
authors: Affiliations of authors: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China (SX, X-GL), Department of Neurosurgery (SX, JW, FW, L-YK, X-YL, EN, KG, TD, YY, FFL, GR, ABH), Department of Biostatistics (WQ), Department of Pathology (GNF), and Department of Experimental Therapeutics (GAC), University of Texas M. D. Anderson Cancer Center, Houston, TX; Baylor College of Medicine, Houston, TX (NKY); Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX (VF). aheimber@mdanderson.org.
authors: Amy B
authors: AB
authors: Heimberger
mesh_terms: D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000276:immunology* / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; C529102:Mirn142 microRNA, mouse; D053773:Transforming Growth Factor beta1