| Autor: |
Shuyin Duan, Junxia Li, Jiaqi Tian, Haoyu Yin, Qingfeng Zhai, Yongjun Wu, Sanqiao Yao, Lin Zhang |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Molecular Therapy: Oncolytics, Vol 15, Iss , Pp 69-78 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2372-7705 |
| DOI: |
10.1016/j.omto.2019.08.010 |
| Popis: |
Autophagy is essential for cellular metabolism and plays pivotal roles in carcinogenesis, while excessive autophagy induces toxicity and cell death. Our previous studies have suggested that let-7a-5p/BCL-xL might regulate autophagy in lung cancer, but the regulatory mechanism is unclear. The central goal of the study was to figure out the role of let-7a-5p/BCL-xL in the initiation of autophagy and its effect on the migration, invasion, and proliferation of A549 cells as well as its therapeutic potential in lung cancer. Based on the genome-wide expression profiles of lung cancer, BCL-xL and let-7a-5p were found to be dysregulated and negatively correlated in lung adenocarcinoma, which was associated with the survival of lung cancer. The crosstalk between BCL-xL and let-7a-5p was then investigated using dual-luciferase reporter assay, and it was found to suppress the migration and invasion of A549 cells. Further, we found that the crosstalk between BCL-xL and let-7a-5p could lead to toxic autophagy and cell death through activating the PI3K-signaling pathway, which was independent of apoptosis or pyroptosis. These findings indicate that let-7a-5p is a sensitive initiator for toxic autophagy in A549 lung cancer cells and is an appealing target for lung cancer therapy. Keywords: lung adenocarcinoma, toxic autophagy, apoptosis, BCL-xL, let-7a-5p |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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