MDM2 promotes epithelial–mesenchymal transition through activation of Smad2/3 signaling pathway in lung adenocarcinoma
Autor: | Yiwen Xuan, Guibin Qiao, Ming Liao, Zhu'an Ou, Zhe He, Yong Tang, Qihang Zhu, Guilin Yin |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
A549 cell Small interfering RNA Cell growth Chemistry SMAD Transfection enzymes and coenzymes (carbohydrates) 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Oncology Cell culture 030220 oncology & carcinogenesis Cancer research Pharmacology (medical) Epithelial–mesenchymal transition Mothers against decapentaplegic neoplasms |
Zdroj: | OncoTargets and Therapy. 12:2247-2258 |
ISSN: | 1178-6930 |
Popis: | Background Mouse double minute 2 (MDM2) contributes to cancer metastasis and epithelial-mesenchymal transition (EMT). This study aimed to investigate small mothers against decapentaplegic (Smad) signaling in MDM2-mediated EMT in lung adenocarcinoma (LAC). Materials and methods Expression patterns of MDM2 in LAC tissues, adjacent tissues, and cell lines (BEAS-2B, PC9, H1975, and A549) were detected. We then overexpressed MDM2 in PC9 cells and knocked it down in H1975 cells. To explore whether MDM2 activates EMT through the Smad2/3 signaling pathway, Smad2 and Smad3 were also silenced by siRNA in H1975 cells. Male BALB/c nude mice were used in in vivo model to validate the effects of MDM2 on LAC cells. Results MDM2 was significantly upregulated in LAC tissues compared with adjacent tissues. The expression of MDM2 was relatively higher in PC9 cells and relatively lower in H1975 cells compared with A549 cells. Overexpression of MDM2 significantly increased cell proliferation, migration, and invasion in LAC cells, while inhibiting apoptosis in PC9 cells. On the contrary, silencing of MDM2 significantly inhibited the expression of EMT-related genes N-cadherin and vimentin, while promoting the expression of E-cadherin and β-catenin. In vivo, MDM2 knockdown inhibited tumor growth. In addition, the expression of Smad2/3 was correlated with MDM2 in H1975 cells transfected with Smad2 and Smad3 siRNAs, which inhibited EMT progress. Conclusion MDM2 can activate the Smad2/3 signaling pathway, which promotes the proliferation and EMT progress of LAC cells. |
Databáze: | OpenAIRE |
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