title: From oncoproteins/tumor suppressors to microRNAs, the newest therapeutic targets for pulmonary arterial hypertension.
abstract: Pulmonary arterial hypertension (PAH) is a disease of the pulmonary vasculature characterized by constricted and remodeled pulmonary arteries. This phenomenon is associated with enhanced pulmonary artery smooth muscle cells proliferation and suppressed apoptosis, metabolism shift, inflammation, and several other features that are considered as hallmarks of cancer. Since oncogenes, tumor suppressors, and miRNAs are the major regulators of signaling in the cancer phenotype, we studied if the same type of regulation is operative in PAH. From the discovery of BMPR2 mutation in familial forms of PAH, oncogenic pathways activation like MAPK were identified. Recently, the Src/STAT3/Pim1 axis was also described as playing a critical role in PAH pathogenesis. Moreover, through the down-regulation of miR-204, STAT3 enhances a positive feedback loop sustaining its own activation, showing that miRNA regulation is critical in PAH. Taken together, targeting oncoproteins or miRNAs appear as new therapeutic strategies for PAH. Several oncoprotein inhibitors are already in trials for cancer and could be soon available for PAH. Concerning miRNAs, the youth of this area makes therapies less achievable soon but not less interesting.
authors.affiliation: Department of Medicine, Laval University, Centre de Recherche du CHUQ, Hôtel-Dieu de Québec, Québec, QC, Canada.
authors.forename: Roxane
authors.initials: R
authors.lastname: Paulin
authors.forename: Audrey
authors.initials: A
authors.lastname: Courboulin
authors.forename: Marjorie
authors.initials: M
authors.lastname: Barrier
authors.forename: Sébastien
authors.initials: S
authors.lastname: Bonnet
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D020935:MAP Kinase Signaling System / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051573:Proto-Oncogene Proteins c-pim-1 / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C549404:MIRN204 microRNA, human; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D025521:Tumor Suppressor Proteins; D019061:src-Family Kinases; C496634:PIM1 protein, human; D051573:Proto-Oncogene Proteins c-pim-1; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II