OncoTargets and Therapy (Aug 2020)
LncRNA TBX5-AS1 Regulates the Tumor Progression Through the PI3K/AKT Pathway in Non-Small Cell Lung Cancer
Abstract
Qing-hai Qu,1,* Shui-zheng Jiang,2,* Xin-ying Li3 1Department of Blood Transfusion, Weifang Yidu Center Hospital, Weifang Medical University, Qingzhou, Shandong 262500, People’s Republic of China; 2Calling Ethos Construction Transfusion, Weifang Yidu Center Hospital, Weifang Medical University, Qingzhou, Shandong 262500, People’s Republic of China; 3Department of Conservative Dentistry and Endodontics, Weifang Dental Hospital, Qingzhou, Shandong 262500, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing-hai Qu Email [email protected]: 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.Keywords: non-small cell lung cancer, long non-coding RNAs, T-box transcription factor 5 antisense RNA 1, aggressive phenotype, PI3K/AKT pathway
