Metformin mediated microRNA-7 upregulation inhibits growth, migration, and invasion of non-small cell lung cancer A549 cells
| Autor: | Jing-Ying Dong, Dan Chen, Lihong Chen, Ya-Nan Zhao, Ji Liu, Xiaolong Yang, Heng Peng, Wenbing Wu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Cancer Research Lung Neoplasms endocrine system diseases growth Cell Apoptosis microRNA-7 migration 03 medical and health sciences 0302 clinical medicine Cell Movement Carcinoma Non-Small-Cell Lung medicine Biomarkers Tumor Tumor Cells Cultured Preclinical Reports Humans Hypoglycemic Agents Pharmacology (medical) Neoplasm Invasiveness Protein kinase B PI3K/AKT/mTOR pathway non-small cell lung cancer Cell Proliferation Pharmacology A549 cell Cell growth Chemistry AMPK nutritional and metabolic diseases respiratory system invasion Metformin Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research medicine.drug Signal Transduction |
| Zdroj: | Anti-Cancer Drugs |
| ISSN: | 1473-5741 0959-4973 |
| Popis: | Metformin, a medication widely used in the treatment of type 2 diabetes mellitus, has a possible antitumor effect in type 2 diabetes mellitus patients. MicroRNA-7 is a significant microRNA in non-small cell lung cancer. Metformin has an inhibitory effect on lung cancer and regulates the expression of certain microRNAs, but there is no report connecting metformin with microRNA-7 in lung cancer. Thus, we used qPCR to measure microRNA-7 expression in A549 non-small cell lung cancer cells treated with metformin. We used CCK8, cell scratch, and Transwell assays to test the growth, migration, and invasion of A549 cells. Western blotting was used to measure the expression level of relevant proteins in A549 cells. We found that microRNA-7 was dramatically upregulated by metformin via AMPK in a dose- and time-dependent manner. Both metformin and microRNA-7 mimic reduced A549 cell growth, migration, and invasion. Metformin downregulated the levels of p-NF-κB p65, p-Erk1/2, p-AKT, and p-mTOR proteins. The treatment with the microRNA-7 mimic had the same result. The decrease of these proteins caused the inhibition of A549 cell growth, migration, and invasion. Our discovery revealed that metformin, via increasing the expression of microRNA-7 mediated by AMPK, regulates the AKT/mTOR, MAPK/Erk, and NF-κB signaling pathways, thereby suppressing A549 cell growth, migration, and invasion. |
| Databáze: | OpenAIRE |
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