OncoTargets and Therapy (Jul 2020)
LncRNA TTN-AS1 Promotes Progression of Non-Small Cell Lung Cancer via Regulating miR-491-5p/ZNF503 Axis
Abstract
Guanbin Qi, Lei Li Department of Respiratory and Critical Care Medicine, Huaihe Hospital, Henan University, Kaifeng, Henan 475000, People’s Republic of ChinaCorrespondence: Lei LiDepartment of Respiratory and Critical Care Medicine, Huaihe Hospital, Henan University, No. 115, Ximen Street, Kaifeng City, Henan Province 475000, People’s Republic of ChinaTel +86-371-23906701Email [email protected]: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with high mortality worldwide. Long non-coding RNA (lncRNA) TTN antisense RNA1 (TTN-AS1) has been demonstrated to play a crucial role in a variety of cancers. This study was designed to investigate the function and molecular mechanism of lncRNA TTN-AS1 in NSCLC.Methods: The expression levels of TTN-AS1, miR-491-5p and zinc finger protein 503 (ZNF503) were examined by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot assay, respectively. Cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell migration and invasion were assessed by transwell assay. Epithelial-to-mesenchymal transition (EMT)-related proteins were measured using Western blot assay. The relationship between TTN-AS1, miR-491-5p and ZNF503 was predicted by starBase2.0 and confirmed by dual-luciferase reporter assay. Xenograft tumor experiment was conducted to analyze the tumor growth in vivo.Results: The levels of TTN-AS1 and ZNF503 were up-regulated, while miR-491-5p expression was reduced in NSCLC tissues and cells. Knockdown of TTN-AS1 or ZNF503 suppressed cell proliferation, migration, invasion and EMT in NSCLC cells. Overexpression of ZNF503 reversed the effect of TTN-AS1 silencing on NSCLC progression. TTN-AS1 could modulate the expression of ZNF503 via sponging miR-491-5p. Furthermore, TTN-AS1 induced tumor growth in vivo.Conclusion: Inhibition of TTN-AS1 hindered cell proliferation, migration, invasion and EMT in NSCLC cells by modulating miR-491-5p/ZNF503 axis, providing a promising biomarker for NSCLC treatment.Keywords: TTN-AS1, miR-491-5p, ZNF503, progression, non-small cell lung cancer
