論文 - 詳細
| RRC ID | 35947 |
|---|---|
| 著者 | Katsura A, Suzuki HI, Ueno T, Mihira H, Yamazaki T, Yasuda T, Watabe T, Mano H, Yamada Y, Miyazono K. |
| タイトル | MicroRNA-31 is a positive modulator of endothelial-mesenchymal transition and associated secretory phenotype induced by TGF-β. |
| ジャーナル | Genes Cells |
| Abstract |
Transforming growth factor-β (TGF-β) plays central roles in endothelial-mesenchymal transition (EndMT) involved in development and pathogenesis. Although EndMT and epithelial-mesenchymal transition are similar processes, roles of microRNAs in EndMT are largely unknown. Here, we report that constitutively active microRNA-31 (miR-31) is a positive regulator of TGF-β-induced EndMT. Although the expression is not induced by TGF-β, miR-31 is required for induction of mesenchymal genes including α-SMA, actin reorganization and MRTF-A activation during EndMT. We identified VAV3, a regulator of actin remodeling and MRTF-A activity, as a miR-31 target. Global transcriptome analysis further showed that miR-31 positively regulates EndMT-associated unique secretory phenotype (EndMT-SP) characterized by induction of multiple inflammatory chemokines and cytokines including CCL17, CX3CL1, CXCL16, IL-6 and Angptl2. As a mechanism for this phenomenon, TGF-β and miR-31 suppress Stk40, a negative regulator of NF-κB pathway. Interestingly, TGF-β induces alternative polyadenylation (APA)-coupled miR-31-dependent Stk40 suppression without concomitant miR-31 induction, and APA-mediated exclusion of internal poly(A) sequence in Stk40 3'UTR enhances target efficiency of Stk40. Finally, miR-31 functions as a molecular hub to integrate TGF-β and TNF-α signaling to enhance EndMT. These data confirm that constitutively active microRNAs, as well as inducible microRNAs, serve as phenotypic modifiers interconnected with transcriptome dynamics during EndMT. |
| 巻・号 | 21(1) |
| ページ | 99-116 |
| 公開日 | 2016-1-1 |
| DOI | 10.1111/gtc.12323 |
| PMID | 26663584 |
| MeSH | 3' Untranslated Regions / genetics Actins / metabolism Animals Base Sequence Cell Line Endothelial Cells / drug effects Endothelial Cells / metabolism Endothelium / cytology Endothelium / drug effects* Endothelium / metabolism Epithelial-Mesenchymal Transition / drug effects* Epithelial-Mesenchymal Transition / genetics Gene Expression Regulation / drug effects Gene Regulatory Networks / drug effects Mesoderm / cytology Mesoderm / drug effects* Mesoderm / metabolism* Mice MicroRNAs / genetics MicroRNAs / metabolism* Molecular Sequence Data Phenotype Polyadenylation / drug effects Proto-Oncogene Proteins c-vav / metabolism Secretory Pathway / drug effects* Trans-Activators / metabolism Transcriptome / drug effects Transcriptome / genetics Transforming Growth Factor beta / pharmacology* Tumor Necrosis Factor-alpha / pharmacology |
| IF | 1.655 |
| 引用数 | 32 |
| WOS 分野 | GENETICS & HEREDITY CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pENTR4-H1 (RDB04395) CS-RfA-EG (RDB04391) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393). |