miR‑505 inhibits cell growth and EMT by targeting MAP3K3 through the AKT‑NFκB pathway in NSCLC cells
| Autor: | Huaping Tang, Qiaojie Bi, Weihong Lv, Yueqin Hao, Wenxin Sun |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Lung Neoplasms medicine.disease_cause Mice 0302 clinical medicine Cell Movement Genes Reporter Carcinoma Non-Small-Cell Lung Neoplasm Metastasis Tumor Stem Cell Assay Chemistry Cell Cycle NF-kappa B Articles General Medicine Middle Aged Cell cycle Gene Expression Regulation Neoplastic 030220 oncology & carcinogenesis Female RNA Interference Signal Transduction microRNA-505 Adult Epithelial-Mesenchymal Transition proliferation MAP3K3 MAP Kinase Kinase Kinase 3 03 medical and health sciences Cell Line Tumor microRNA Genetics medicine Animals Humans Gene silencing Protein kinase B non-small cell lung cancer Aged Cell Proliferation Neoplasm Staging Oncogene Cell growth mitogen-activated protein kinase kinase kinase 3 AKT/nuclear factor-κB MicroRNAs 030104 developmental biology Cancer research Carcinogenesis Proto-Oncogene Proteins c-akt |
| Zdroj: | International Journal of Molecular Medicine |
| ISSN: | 1791-244X 1107-3756 |
| DOI: | 10.3892/ijmm.2018.4041 |
| Popis: | MicroRNAs (miRNAs) are short non-coding RNAs, which generally regulate gene expression at the post-transcriptional level. Dysregulation of miRNAs has been reported in numerous cancer types, including lung cancer. In the present study, the role of miR-505 in non-small cell lung cancer (NSCLC) cells was investigated. miR-505 served a tumor suppressor role in NSCLC cells. By reverse transcriptase-quantitative polymerase chain reaction detection, it was demonstrated that miR-505 was downregulated in NSCLC tissues and cell lines, which is negatively associated with large tumor size, Tumor-Node-Metastasis stage and distant metastasis in patients with NSCLC. Functional studies revealed that miR-505 inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition progress in vitro and tumor growth in vivo. Mechanically, mitogen-activated protein kinase kinase kinase 3 (MAP3K3) was identified as a direct target of miR-505 by binding to its 3′untranslated region and demonstrated to mediate the tumor suppressor roles of miR-505 in NSCLC cells. The effect of miR-505 on the activation of AKT/nuclear factor-κB (NFκB) pathway, which was downstream targets of MAP3K3, was further analyzed by western blot analysis and immunofluorescence analyses. The data demonstrated the inhibition of the AKT/NFκB pathway upon overexpressing miR-505 and the activation of AKT/NFκB pathway upon silencing miR-505. Collectively, the data revealed the novel role and target of miR-505 in NSCLC cells, which may provide novel insights regarding its role in the carcinogenesis of NSCLC and its potential values for clinical applications. |
| Databáze: | OpenAIRE |
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