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RNA-binding motif protein 47 inhibits Nrf2 activity to suppress tumor growth in lung adenocarcinoma
Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo, Japan..
Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo, Japan..
Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo, Japan..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2016 (English)In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 35, no 38, 5000-5009 p.Article in journal (Refereed) Published
Abstract [en]

RNA-binding proteins provide a new layer of posttranscriptional regulation of RNA during cancer progression. We identified RNA-binding motif protein 47 (RBM47) as a target gene of transforming growth factor (TGF)-beta in mammary gland epithelial cells (NMuMG cells) that have undergone the epithelial-to-mesenchymal transition. TGF-beta repressed RBM47 expression in NMuMG cells and lung cancer cell lines. Expression of RBM47 correlated with good prognosis in patients with lung, breast and gastric cancer. RBM47 suppressed the expression of cell metabolism-related genes, which were the direct targets of nuclear factor erythroid 2-related factor 2 (Nrf2; also known as NFE2L2). RBM47 bound to KEAP1 and Cullin 3 mRNAs, and knockdown of RBM47 inhibited their protein expression, which led to enhanced binding of Nrf2 to target genomic regions. Knockdown of RBM47 also enhanced the expression of some Nrf2 activators, p21/CDKN1A and MafK induced by TGF-beta. Both mitochondrial respiration rates and the side population cells in lung cancer cells increased in the absence of RBM47. Our findings, together with the enhanced tumor formation and metastasis of xenografted mice by knockdown of the RBM47 expression, suggested tumor-suppressive roles for RBM47 through the inhibition of Nrf2 activity.

Place, publisher, year, edition, pages
2016. Vol. 35, no 38, 5000-5009 p.
National Category
Cancer and Oncology
URN: urn:nbn:se:uu:diva-305331DOI: 10.1038/onc.2016.35ISI: 000383965300004PubMedID: 26923328OAI: diva2:1037361
Available from: 2016-10-14 Created: 2016-10-14 Last updated: 2016-10-14Bibliographically approved

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