E-GEOD-61910 - Reduced expression of RBM47 enhances Nrf2 activity to promote tumor growth in A549 lung adenocarcinoma cells

Status
Released on 1 March 2016, last updated on 6 March 2016
Organism
Homo sapiens
Samples (8)
Protocols (4)
Description
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 (EMT). 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 Cullin3 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. Effect of shRNA for RBM47 and TGF-beta on gene expression was evaluated by RNA-seq and RBM47-bound RNAs were identified by RIP-seq in A549 cells.
Experiment types
other, RNA-seq of coding RNA 
Contacts
Daizo Koinuma <d-koinuma@umin.ac.jp>, Kazunobu Isogaya, Kohei Miyazono, Masato Morikawa, Satoshi Sakai, Shogo Ehata, Tsubasa Sakurai, Yasuyuki Morishita
Citation
RNA-binding motif protein 47 inhibits Nrf2 activity to suppress tumor growth in lung adenocarcinoma. Sakurai T, Isogaya K, Sakai S, Morikawa M, Morishita Y, Ehata S, Miyazono K, Koinuma D. , PMID:26923328
MINSEQE
Exp. designProtocolsVariablesProcessedSeq. reads
Files
Investigation descriptionE-GEOD-61910.idf.txt
Sample and data relationshipE-GEOD-61910.sdrf.txt
Additional data (1)E-GEOD-61910.additional.1.zip
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