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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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<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Kucuksayan, Hakan</dc:creator>
  <dc:creator>Akgun, Sakir</dc:creator>
  <dc:creator>Ozes, Osman Nidai</dc:creator>
  <dc:creator>Alikanoglu, Arsenal Sezgin</dc:creator>
  <dc:creator>Yildiz, Mustafa</dc:creator>
  <dc:creator>Dal, Egemen</dc:creator>
  <dc:creator>Akca, Hakan</dc:creator>
  <dc:date>2019-01-01</dc:date>
  <dc:description>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.</dc:description>
  <dc:identifier>https://aperta.ulakbim.gov.trrecord/75021</dc:identifier>
  <dc:identifier>oai:zenodo.org:75021</dc:identifier>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>http://www.opendefinition.org/licenses/cc-by</dc:rights>
  <dc:source>CARCINOGENESIS 40(5) 695-705</dc:source>
  <dc:title>TGF-beta-SMAD-miR-520e axis regulates NSCLC metastasis through a TGFBR2-mediated negative-feedback loop</dc:title>
  <dc:type>info:eu-repo/semantics/article</dc:type>
  <dc:type>publication-article</dc:type>
</oai_dc:dc>
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