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From oncoproteins/tumor suppressors to microRNAs, the newest therapeutic targets for pulmonary arterial hypertension

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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.

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Acknowledgments

We want to thank the “Société Québécoise d'Hypertension Arterielle” for the scholarship attributed to RP. This work was supported by the Heart and Stroke Foundation of Canada (HSFC), the Canadian Institute for Health Research (CIHR), and the Canadian Research Chair (CRC) to SB.

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Authors and Affiliations

  1. Department of Medicine, Laval University, Centre de Recherche du CHUQ, Hôtel-Dieu de Québec, Québec, QC, Canada

    Roxane Paulin, Audrey Courboulin, Marjorie Barrier & Sébastien Bonnet

  2. Centre de Recherche du CHUQ, Hôtel-Dieu de Québec, 10 Rue McMahon, Québec, QC, G1R 2J6, Canada

    Sébastien Bonnet

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  1. Roxane Paulin
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  2. Audrey Courboulin
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  3. Marjorie Barrier
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  4. Sébastien Bonnet
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Correspondence to Sébastien Bonnet.

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Roxane Paulin and Audrey Courboulin equally contributed.

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Paulin, R., Courboulin, A., Barrier, M. et al. From oncoproteins/tumor suppressors to microRNAs, the newest therapeutic targets for pulmonary arterial hypertension. J Mol Med 89, 1089–1101 (2011). https://doi.org/10.1007/s00109-011-0788-5

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  • DOI: https://doi.org/10.1007/s00109-011-0788-5

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