LncRNA TBX5-AS1 Regulates the Tumor Progression Through the PI3K/AKT Pathway in Non-Small Cell Lung Cancer

Autor:	Shui-Zheng Jiang, Qing-Hai Qu, Xin-Ying Li
Rok vydání:	2020
Předmět:	0301 basic medicine Regulation of gene expression Gene knockdown medicine.diagnostic_test Transfection Biology Flow cytometry 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Oncology Tumor progression 030220 oncology & carcinogenesis Cancer research medicine Pharmacology (medical) Viability assay Protein kinase B PI3K/AKT/mTOR pathway
Zdroj:	OncoTargets and Therapy. 13:7949-7961
ISSN:	1178-6930
DOI:	10.2147/ott.s255195
Popis:	Purpose Long non-coding RNAs (lncRNAs) have been reported to play important roles in tumor biology. In this study, we aimed to investigate the effects of T-box transcription factor 5 antisense RNA 1 (TBX5-AS1) on aggressive phenotypes of non-small cell lung cancer (NSCLC) cells and explore its regulatory pathway. Methods The expression of TBX5-AS1 in tissues, plasma, and cells was determined by qRT-PCR. Cell viability, proliferation, migration, invasion, and apoptosis were assessed using MTT, colony formation, wound-healing, Transwell, and flow cytometry assay, respectively. Western blot analysis was performed to measure the expression of apoptosis-related proteins. Besides, transfected cells were exposed to PI3K activator (740Y-P) to verify the regulatory pathway. Results TBX5-AS1 expression was down-regulated in NSCLC tissues, plasma, and cells, and associated with lymph node metastasis and histological grade. Overexpression of TBX5-AS1 inhibited cell viability, colony formation, migration, and invasion, while it promoted apoptosis. Conversely, knockdown of TBX5-AS1 showed the completely opposite results. Additionally, western blot showed that the phosphorylation of PI3K and AKT was stimulated by TBX5-AS1 knockdown and suppressed by TBX5-AS1 overexpression. The addition of 740Y-P in transfected cells reversed the TBX5-AS1-induced inhibition of PI3K and AKT phosphorylation and effects on aggressive phenotypes of NSCLC cells. Conclusion The study confirmed the down-regulation of TBX5-AS1 in patients with NSCLC and its association with the progression. We innovatively proposed a possible model of TBX5-AS1-mediated gene regulation in NSCLC progression that TBX5-AS1 inhibited the aggressive phenotypes of NSCLC cells through inactivating the PI3K/AKT pathway. This finding provided a novel insight into NSCLC pathogenesis.
Databáze:	OpenAIRE
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