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TGF-β–SMAD–miR-520e axis regulates NSCLC metastasis through a TGFBR2-mediated negative-feedback loop       
Yazarlar
Dr. Öğr. Üyesi Hakan KÜÇÜKSAYAN Dr. Öğr. Üyesi Hakan KÜÇÜKSAYAN
Kastamonu Üniversitesi, Türkiye
Şakir Akgün
Türkiye
Osman Nidai Özeş
Türkiye
Mustafa Yıldız
Türkiye
Arsenal Sezgin Alikanoğlu
Türkiye
Egemen Dal
Hakan Akça
Pamukkale Üniversitesi, Türkiye
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
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı CARCINOGENESIS
Dergi ISSN 0143-3334
Dergi Tarandığı Indeksler SCI
Makale Dili Türkçe
Basım Tarihi 05-2019
Cilt No 40
Sayı 5
Sayfalar 695 / 705
Doi Numarası 10.1093/carcin/bgy166
Makale Linki http://dx.doi.org/10.1093/carcin/bgy166