Smad3-related miRNAs regulated oncogenic TRIB2 promoter activity to effectively suppress lung adenocarcinoma growth

Yan-Xia Zhang1, Yun-Fei Yan1, Yue-Mei Liu1

  • 1Key Laboratory of Tumor Molecular Biology in Binzhou Medical University, Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, ShanDong, P.R.China.

Cell Death & Disease
|December 23, 2016
PubMed

Insights

MicroRNAs miR-206 and miR-140 act as tumor suppressors in lung adenocarcinoma. They inhibit cancer cell proliferation and metastasis by targeting TRIB2 and regulating TGF-β1 signaling.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • MicroRNAs (miRNAs) and Smad3 are crucial in transforming growth factor-β1 (TGF-β1) signaling.
  • Dysregulation of these factors contributes to various diseases, including lung adenocarcinoma.

Purpose of the Study:

  • To investigate the roles of Smad3-regulated miRNAs in lung adenocarcinoma.
  • To understand their impact on apoptosis, proliferation, and metastasis.

Main Methods:

  • Treatment of lung adenocarcinoma cells with miR-206 or miR-140.
  • Analysis of Smad3, phospho-SMAD3 (p-Smad3), and TGF-β1 expression.
  • Investigation of tribbles homolog 2 (TRIB2) promoter activity.
  • In vitro and in vivo proliferation and metastasis assays.
  • Correlation analysis with patient survival data.

Main Results:

  • miR-206 and miR-140 decreased Smad3 and p-Smad3 levels, suggesting a feedback loop with TGF-β1.
  • These miRNAs suppressed lung adenocarcinoma cell proliferation and induced apoptosis by inhibiting p-Smad3/Smad3 and TRIB2.
  • Higher TRIB2 levels correlated with poorer patient survival, indicating its oncogenic role.
  • miR-206 and miR-140 suppressed metastasis by regulating epithelial-mesenchymal transition (EMT)-related factors.

Conclusions:

  • miR-206 and miR-140 function as tumor suppressors in lung adenocarcinoma.
  • They induce cell death and inhibit proliferation by targeting the oncogenic TRIB2 promoter via p-Smad3.
  • These miRNAs also suppress metastasis by modulating EMT.

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