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Transforming growth factor-beta (TGF-beta) pathway plays crucial roles during the carcinogenesis and metastasis. TGF-beta receptor 2 (TGFBR2) is a key molecule for the regulation of TGF-beta pathway and frequently downregulated or lost in several cancer types including non-small cell lung cancer (NSCLC), and TGF-beta 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-beta dramatically increased the expression of miR-520e, which targeted and downregulated TGFBR2, and the suppression of miR-520e significantly impaired TGF-beta-induced TGFBR2 downregulation. Chromatin immunoprecipitation-PCR experiments further showed that miR-520e is transcriptionally induced by SMAD2/3 in response to TGF-beta. Our findings reveal a novel negative-feedback mechanism in TGF-beta signaling and the expression level of miR-520e could be a predictive biomarker for NSCLC metastasis. We demonstrate that low TGFBR2 and high miR-520e expression correlated with increased metastatic capacity of non-small cell lung cancer cells. Furthermore, our findings provide a novel mechanism by which miR-520e-mediated the self-limiting of transforming growth factor-beta in metastasis of lung cancer cells. C1 [Kucuksayan, Hakan; Akgun, Sakir; Akca, Hakan] Pamukkale Univ, Sch Med, Med Biol Dept, Denizli, Turkey. [Ozes, Osman Nidai] ALTAY Biopharma, San Bruno, CA USA. [Alikanoglu, Arsenal Sezgin] Antalya Training & Res Hosp, Pathol Dept, Antalya, Turkey. [Yildiz, Mustafa] Antalya Training & Res Hosp, Med Oncol, Antalya, Turkey. [Dal, Egemen] Pamukkale Univ, Fac Med, Denizli, Turkey. |
