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TGF-beta-SMAD-miR-520e axis regulates NSCLC metastasis through a TGFBR2-mediated negative-feedback loop

Kucuksayan, Hakan; Akgun, Sakir; Ozes, Osman Nidai; Alikanoglu, Arsenal Sezgin; Yildiz, Mustafa; Dal, Egemen; Akca, Hakan


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{
  "DOI": "10.1093/carcin/bgy166", 
  "abstract": "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.", 
  "author": [
    {
      "family": "Kucuksayan", 
      "given": " Hakan"
    }, 
    {
      "family": "Akgun", 
      "given": " Sakir"
    }, 
    {
      "family": "Ozes", 
      "given": " Osman Nidai"
    }, 
    {
      "family": "Alikanoglu", 
      "given": " Arsenal Sezgin"
    }, 
    {
      "family": "Yildiz", 
      "given": " Mustafa"
    }, 
    {
      "family": "Dal", 
      "given": " Egemen"
    }, 
    {
      "family": "Akca", 
      "given": " Hakan"
    }
  ], 
  "container_title": "CARCINOGENESIS", 
  "id": "75021", 
  "issue": "5", 
  "issued": {
    "date-parts": [
      [
        2019, 
        1, 
        1
      ]
    ]
  }, 
  "page": "695-705", 
  "title": "TGF-beta-SMAD-miR-520e axis regulates NSCLC metastasis through a TGFBR2-mediated negative-feedback loop", 
  "type": "article-journal", 
  "volume": "40"
}
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