TGF-β–SMAD–miR-520e axis regulates NSCLC metastasis through a TGFBR2-mediated negative-feedback loop
Yazarlar (7)
Dr. Öğr. Üyesi Hakan KÜÇÜKSAYAN Kastamonu Üniversitesi, Türkiye
Şakir Akgün Pamukkale Üniversitesi, Türkiye
Osman Nidai Özeş
Altay Biopharma, Türkiye
Altay Biopharma, Türkiye
Mustafa Yıldız Antalya Training And Research Hospital, Türkiye
Arsenal Sezgin Alikanoğlu Antalya Training And Research Hospital, Türkiye
Egemen Dal Pamukkale Üniversitesi, Türkiye
Prof. Dr. Hakan Akça Pamukkale Üniversitesi, Türkiye
| Makale Türü | Özgün Makale (SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale) | ||
| Dergi Adı | Carcinogenesis (Q2) | ||
| Dergi ISSN | 0143-3334 Wos Dergi Scopus Dergi | ||
| Dergi Tarandığı Indeksler | SCI | ||
| Makale Dili | Türkçe | Basım Tarihi | 11-2018 |
| Cilt / Sayı / Sayfa | 40 / 5 / 695–705 | DOI | 10.1093/carcin/bgy166 |
| Makale Linki | http://dx.doi.org/10.1093/carcin/bgy166 | ||
| Özet |
| 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. |
| Anahtar Kelimeler |
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| Web of Science | 12 |
| Scopus | 15 |
| Google Scholar | 24 |