Pathologically decreased expression of miR-193a contributes to metastasis by targeting WT1-E-cadherin axis in non-small cell lung cancers
| Autor: | Bin Zhou, Chengshui Chen, Junjie Chen, Chunjing Wang, Jianbo Wu, Zhonggai Wang, Shenmeng Gao, Kate Huang, Haiying Li, Huxiang Zhang, Zhijie Yu |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Pathology Lung Neoplasms Cell MiR-193a Metastasis Epigenesis Genetic Mice 0302 clinical medicine Cell Movement Carcinoma Non-Small-Cell Lung Neoplasm Metastasis Cadherins lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Gene Expression Regulation Neoplastic medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Erratum Signal Transduction medicine.medical_specialty Epithelial-Mesenchymal Transition Down-Regulation Biology Wilm’s tumor-1 lcsh:RC254-282 03 medical and health sciences Antigens CD Cell Line Tumor microRNA medicine Animals Humans Epithelial–mesenchymal transition Lung cancer WT1 Proteins Cell Proliferation Cadherin Cell growth Research E-cadherin DNA Methylation medicine.disease MicroRNAs 030104 developmental biology Epithelial-to-mesenchymal transition A549 Cells Cancer research Ectopic expression Neoplasm Transplantation |
| Zdroj: | Journal of Experimental & Clinical Cancer Research, Vol 35, Iss 1, Pp 1-15 (2016) Journal of Experimental & Clinical Cancer Research : CR |
| ISSN: | 1756-9966 |
| Popis: | Background The metastatic cascade is a complex and multistep process with many potential barriers. Recently, miR-193a has been reported to be a suppressive miRNA in multiple types of cancers, but its underlying anti-oncogenic activity in non-small cell lung cancers (NSCLC) is not fully elucidated. Methods The expressions of miR-193a (miR-193a-5p) in human lung cancer tissues and cell lines were detected by real-time PCR. Dual-luciferase reporter assay was used to identify the direct target of miR-193a. Cell proliferation, apoptosis, and metastasis were assessed by CCK-8, flow cytometry, and Transwell assay, respectively. Results The expression of miR-193a in lung cancer tissues was decreased comparing to adjacent non-tumor tissues due to DNA hypermethylation in lung cancer tissues. Ectopic expression of miR-193a inhibited cell proliferation, colony formation, migration, and invasion in A549 and H1299 cells. Moreover, overexpression of miR-193a partially reversed tumor growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) in NSCLC cells. Mechanistically, miR-193a reduced the expression of WT1, which negatively regulated the protein level of E-cadherin, suggesting that miR-193a might prevent EMT via modulating WT1-E-cadherin axis. Importantly, knockdown of WT1 resembled the anti-cancer activity by miR-193a and overexpression of WT1 partially reversed miR-193a-induced anti-cancer activity, indicating that WT1 plays an important role in miR-193a-induced anti-cancer activity. Finally, overexpression of miR-193a decreased the growth of tumor xenografts in mice. Conclusion Collectively, our results have revealed an important role of miR-193a-WT1-E-cadherin axis in metastasis, demonstrated an important molecular cue for EMT, and suggested a therapeutic strategy of restoring miR-193a expression in NSCLC. Electronic supplementary material The online version of this article (doi:10.1186/s13046-016-0450-8) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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