TGF-β–SMAD–miR-520e axis regulates NSCLC metastasis through a TGFBR2-mediated negative-feedback loop
| Autor: | Sakir Akgun, Osman N. Ozes, Egemen Dal, Hakan Kucuksayan, Hakan Akca, Arsenal Sezgin Alikanoglu, Mustafa Yildiz |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Lung Neoplasms Apoptosis Smad2 Protein Biology medicine.disease_cause Metastasis Transforming Growth Factor beta1 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cell Movement Carcinoma Non-Small-Cell Lung Biomarkers Tumor medicine Humans Neoplasm Invasiveness Smad3 Protein Receptor Cell Proliferation Feedback Physiological Regulation of gene expression Receptor Transforming Growth Factor-beta Type II Cancer General Medicine medicine.disease Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology A549 Cells Lymphatic Metastasis 030220 oncology & carcinogenesis Cancer research Signal transduction Carcinogenesis Signal Transduction Transforming growth factor |
| Zdroj: | Carcinogenesis. 40:695-705 |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/bgy166 |
| Popis: | Transforming growth factor-β (TGF-β) pathway plays crucial roles during the carcinogenesis and metastasis. TGF-β receptor 2 (TGFBR2) is a key molecule for the regulation of TGF-β pathway and frequently downregulated or lost in several cancer types including non-small cell lung cancer (NSCLC), and TGF-β pathway is often regulated by negative-feedback mechanisms, but little is known about the mechanism of TGFBR2 downregulation in NSCLC. Here, we found that the expression of miR-520e is upregulated in metastatic tumor tissues compared with non-metastatic ones, and its expression is inversely correlated with that of TGFBR2 in clinical samples. We also discovered that TGF-β dramatically increased the expression of miR-520e, which targeted and downregulated TGFBR2, and the suppression of miR-520e significantly impaired TGF-β-induced TGFBR2 downregulation. Chromatin immunoprecipitation–PCR experiments further showed that miR-520e is transcriptionally induced by SMAD2/3 in response to TGF-β. Our findings reveal a novel negative-feedback mechanism in TGF-β signaling and the expression level of miR-520e could be a predictive biomarker for NSCLC metastasis. |
| Databáze: | OpenAIRE |
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