Modulation of NF-κB/miR-21/PTEN Pathway Sensitizes Non-Small Cell Lung Cancer to Cisplatin
| Autor: | Yan Tan, Weiwei Ying, Wei Gu, Yicheng Di, Zhenhua Yang, Surong Fang |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Lung Neoplasms Science Antineoplastic Agents Apoptosis Biology Downregulation and upregulation Carcinoma Non-Small-Cell Lung Cell Line Tumor microRNA medicine Humans PTEN Luciferase Viability assay Aged Cisplatin A549 cell Multidisciplinary NF-kappa B PTEN Phosphohydrolase Middle Aged Molecular biology Up-Regulation MicroRNAs HEK293 Cells Cancer research biology.protein Medicine Research Article medicine.drug |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 3, p e0121547 (2015) |
| ISSN: | 1932-6203 |
| Popis: | BackgroundPlatinum-based chemotherapy is a standard strategy for non-small cell lung cancer (NSCLC), while chemoresistance remains a major therapeutic challenge in current clinical practice. Our present study was aimed to determine whether inhibition of the NF-κB/miR-21/PTEN pathway could increase the sensitivity of NSCLC to cisplatin.MethodsThe expression of miR-21 in NSCLC tissues was determined using in situ hybridization. Next, the effect of miR-21 on the sensitivity of A549 cells to cisplatin was determined in vitro. Whether miR-21 regulated PTEN expression was assessed by luciferase assay. Furthermore, whether NF-κB targeted its binding elements in the miR-21 gene promoter was determined by luciferase and ChIP assay. Finally, we measured the cell viability and apoptosis under cisplatin treatment when NF-κB was inhibited.ResultsAn elevated level of miR-21 was observed in NSCLC lung tissues and was related to a short survival time. Exogenous miR-21 promoted cell survival when exposed to cisplatin, while miR-21 inhibition could reverse this process. The RNA and protein levels of PTEN were significantly decreased by exogenous miR-21, and the 3'-untranslated region of PTEN was shown to be a target of miR-21. The expression of miR-21 was regulated by NF-κB binding to its element in the promoter, a finding that was verified by luciferase and ChIP assay. Hence, inhibition of NF-κB by RNA silencing protects cells against cisplatin via decreasing miR-21 expression.ConclusionModulation of the NF-κB/miR-21/PTEN pathway in NSCLC showed that inhibition of this pathway may increase cisplatin sensitivity. |
| Databáze: | OpenAIRE |
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