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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
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.
Abstract:
MicroRNAs (miRNAs) and Smad3, as key transcription factors in transforming growth factor-β1 (TGF-β1) signaling, help regulate various physiological and pathological processes. We investigated the roles of Smad3-regulated miRNAs with respect to lung adenocarcinoma cell apoptosis, proliferation, and metastasis. We observed that Smad3 and phospho-SMAD3 (p-Smad3) were decreased in miR-206- (or miR-140)-treated cells and there might be a feedback loop between miR-206 (or miR-140) and TGF-β1 expression. Smad3-related miRNAs affected tribbles homolog 2 (TRIB2) expression by regulating trib2 promoter activity through the CAGACA box. MiR-206 and miR-140 inhibited lung adenocarcinoma cell proliferation in vitro and in vivo by suppressing p-Smad3/Smad3 and TRIB2. Moreover, lung adenocarcinoma data supported a suppressive role for miR-206/miR-140 and an oncogenic role for TRIB2-patients with higher TRIB2 levels had poorer survival. In summary, miR-206 and miR-140, as tumor suppressors, induced lung adenocarcinoma cell death and inhibited cell proliferation by modifying oncogenic TRIB2 promoter activity through p-Smad3. MiR-206 and miR-140 also suppressed lung adenocarcinoma cell metastasis in vitro and in vivo by regulating EMT-related factors.
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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