Long Non-Coding RNA NNT-AS1 Contributes to Cisplatin Resistance via miR-1236-3p/ATG7 Axis in Lung Cancer Cells

Autor:	Min Guo, Haifeng Wang, Feng Yang, Zhongjie Chen, Dongxiao Ding
Rok vydání:	2020
Předmět:	0301 basic medicine Cisplatin endocrine system diseases Chemistry Cell growth Cell medicine.disease medicine.disease_cause Metastasis 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Oncology Apoptosis health services administration 030220 oncology & carcinogenesis microRNA medicine Cancer research Pharmacology (medical) Lung cancer Carcinogenesis medicine.drug
Zdroj:	OncoTargets and Therapy. 13:3641-3652
ISSN:	1178-6930
Popis:	Purpose Lung cancer is one of the most prevailing human cancers worldwide. Emerging evidence implies that long non-coding RNA nicotinamide nucleotide transhydrogenase-antisense RNA1 (NNT-AS1) is implicated in the tumorigenesis of lung cancer. Herein, we aimed to expose the impact of NNT-AS1 on the drug resistance of lung cancer. Methods Levels of NNT-AS1, microRNA (miR)-1236-3p and autophagy-related gene 7 (ATG7) were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was implemented to detect cell proliferation and the half maximal inhibitory concentration (IC50) of cisplatin (DDP) in vitro. Moreover, flow cytometry was performed to assess cell apoptosis. Cell migration and invasion were examined utilizing transwell assay in lung cancer cells. Besides, levels of ATG7 and cell behavior-related proteins were determined via Western blot. Dual-luciferase reporter assay was administrated to identify the interaction between miR-1236-3p and NNT-AS1 or ATG7. The biological role of NNT-AS1 in DDP resistance of lung cancer was examined by xenograft tumor model in vivo. Results NNT-AS1 and ATG7 were upregulated, whereas miR-1236-3p was curbed in lung cancer tissues and in with or without DDP-resistant cell lines. NNT-AS1 detection significantly constrained cell growth, metastasis, and the IC50 of DDP in A549/DDP and H522/DDP cells. Interestingly, the influence of miR-1236-3p mimic on DDP resistance was overturned via NNT-AS1 upregulation in vitro. Reintroduction of miR-1236-3p inhibitor relieved the effect of ATG7 silencing on DDP sensitivity in A549/DDP and H522/DDP cells. Importantly, NNT-AS1 was a sponge of miR-1236-3p to separate ATG7. Besides, NNT-AS1 silencing enhanced DDP sensitivity of lung cancer in vivo. Conclusion NNT-AS1/miR-1236-3p/ATG7 axis regulated DDP resistance in lung cancer cells and might supply a probable target and prognostic marker in lung cancer treatment.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::6d744d48c6ebe5a00067258710b92540 https://doi.org/10.2147/ott.s237576 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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