miR-138 suppresses the proliferation, metastasis and autophagy of non-small cell lung cancer by targeting Sirt1
| Autor: | Tianzheng Lou, Jiongwei Pan, Zhuo Cao, Ning Zhang, Jinwei Huang, Congying Xie, Bingmu Fang, Zaiting Ye |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male signaling pathway 0301 basic medicine autophagy Cancer Research Epithelial-Mesenchymal Transition miR-138 Biology medicine.disease_cause Metastasis 03 medical and health sciences 0302 clinical medicine Cell Movement Carcinoma Non-Small-Cell Lung Cell Line Tumor medicine Humans Neoplasm Invasiveness Lung cancer non-small cell lung cancer PI3K/AKT/mTOR pathway Aged Cell Proliferation Oncogene Cell growth TOR Serine-Threonine Kinases Cell Cycle Cancer Articles General Medicine Middle Aged Cell cycle medicine.disease Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology Oncology Lymphatic Metastasis 030220 oncology & carcinogenesis mTOR Cancer research Female RNA Long Noncoding Carcinogenesis Signal Transduction |
| Zdroj: | Oncology Reports |
| ISSN: | 1791-2431 1021-335X |
| DOI: | 10.3892/or.2017.5619 |
| Popis: | The present study determined the role and mechanism of miR-138 in non-small cell lung cancer (NSCLC). In total, 45 freshly resected clinical NSCLC tissues were collected. The expression of miR-138 in tissues and cell lines were determined by real-time quantitative PCR. miR-138 mimics were transfected into A549 and Calu-3 cells in vitro, and then the effects of miR-138 on lung cancer cell proliferation, cell cycle, invasion and metastasis were investigated by CCK-8 assay, Transwell and flow cytometry, respectively. The protein expression of the potential target gene Sirt1 in lung cancer cells were determined by western blot analysis. Dual-Luciferase reporter assay was performed to further confirm whether Sirt1 was the target gene of miR-138. The expression of miR-138 was significantly lower in lung cancer tissues and was negatively correlated to the differentiation degree and lymph node metastasis of lung cancer. In vitro experiment results showed that miR-138 inhibited lung cancer cell proliferation, invasion and migration. It was verified that miR-138 could downregulate Sirt1 protein expression, inhibit epithelial-mesenchymal transition (EMT), decrease the activity of AMPK signaling pathway and elevate mTOR phosphorylation level. Dual-Luciferase reporter assay demonstrated that miR-138 could directly regulate Sirt1. Downregulation of Sirt1 alone can also cause the same molecular and biological function changes. Western blot analysis and confocal microscopy results indicated that overexpression of miR-138 or interference of Sirt1 expression could inhibit lung cancer cell autophagy activity possibly through AMPK-mTOR signaling pathway. miR-138 plays a tumor suppressor function in lung cancer. It may inhibit the proliferation, invasion and migration of lung cancer through downregulation of Sirt1 expression and activation of cell autophagy. The downregulation of miR-138 is closely related to the development of lung cancer. |
| Databáze: | OpenAIRE |
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