PMID- 34765296 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211113 IS - 2156-6976 (Print) IS - 2156-6976 (Electronic) IS - 2156-6976 (Linking) VI - 11 IP - 10 DP - 2021 TI - LncRNA NR2F2-AS1 induces epithelial-mesenchymal transition of non-small cell lung cancer by modulating BVR/ATF-2 pathway via regulating miR-545-5p/c-Met axis. PG - 4844-4865 AB - Non-small cell lung cancer (NSCLC) is one type of the most common cancers, which results in the major death worldwide. This study focuses on the understanding of the molecular mechanism of lncRNA NR2F2-AS1 and its regulation on epithelial-mesenchymal transition (EMT) in the development of NSCLC. Expressions of lncRNA NR2F2-AS1, miR-545-5p, c-Met, biliverdin reductase (BVR), ATF-2 and EMT-related markers in NSCLC tissues and cells were measured by western blotting and RT-qPCR assays. The impact of lncRNA NR2F2-AS1 and miR-545-5p on the cell proliferation, migration, invasion and EMT were analyzed by CCK-8, colony formation, wound healing and transwell assays. The interactions among lncRNA NR2F2-AS1, miR-545-5p and c-Met predicted by bioinformatic analysis were evaluated through dual luciferase reporter assay and fluorescence in situ hybridization (FISH). After generating tumor xenografts, immunohistochemistry was utilized to measure the expression of Ki-67 and EMT-related proteins in vivo. Our results showed that lncRNA NR2F2-AS1, c-Met, BVR and ATF-2 were overexpressed while miR-545-5p was silenced in NSCLC tissues and cells. Silencing of lncRNA NR2F2-AS1 or upregulating miR-545-5p significantly inhibited the cell proliferation, migration, invasion and EMT process. The EMT process could be inhibited by suppressing c-Met/BVR/ATF-2 axis. The tumor xenograft experiments demonstrated that the tumor growth and EMT process were significantly inhibited by silencing lncRNA NR2F2-AS1 or overexpression of miR-545-5p in vivo. LncRNA NR2F2-AS1 promoted the NSCLC development through suppressing miR-545-5p to activate EMT process through c-Met/BVR/ATF-2 axis. Our study indicated that lncRNA NR2F2-AS1 and miR-545-5p could be used as potential therapeutic targets to improve NSCLC treatment. CI - AJCR Copyright (c) 2021. FAU - Liu, Cheng AU - Liu C AD - Department of Thoracic Surgery, The Fourth Affiliated Hospital of Harbin Medical University Harbin 150001, Heilongjiang Province, P. R. China. FAU - Li, Qun-Gen AU - Li QG AD - Department of Cardiothoracic Surgery, Heilongjiang Provincial Hospital Affiliated to Harbin Institute of Technology Harbin 150001, Heilongjiang Province, P. R. China. FAU - Zhou, Yang AU - Zhou Y AD - Department of Medical Oncology, Harbin Medical University Cancer Hospital Harbin 150081, Heilongjiang Province, P. R. China. FAU - Cao, Ying-Yue AU - Cao YY AD - Department of Medical Oncology, Harbin Medical University Cancer Hospital Harbin 150081, Heilongjiang Province, P. R. China. FAU - Wei, Zi-Xin AU - Wei ZX AD - Department of Medical Oncology, Harbin Medical University Cancer Hospital Harbin 150081, Heilongjiang Province, P. R. China. FAU - Jin, Ying-Hua AU - Jin YH AD - Department of Medical Oncology, Harbin Medical University Cancer Hospital Harbin 150081, Heilongjiang Province, P. R. China. FAU - Wang, Xin AU - Wang X AD - Department of Medical Oncology, Harbin Medical University Cancer Hospital Harbin 150081, Heilongjiang Province, P. R. China. FAU - Chen, Ying-Ying AU - Chen YY AD - Department of Gastroenterology, The First Affiliated Hospital of Harbin Medical University Harbin 150001, Heilongjiang Province, P. R. China. FAU - Qi, Li AU - Qi L AD - Department of Radiation Oncology, The Second Affiliated Hospital of Harbin Medical University Harbin 150086, Heilongjiang Province, P. R. China. FAU - Geng, Jian-Xiong AU - Geng JX AD - Department of Medical Oncology, Harbin Medical University Cancer Hospital Harbin 150081, Heilongjiang Province, P. R. China. FAU - Liu, Fang AU - Liu F AD - Department of Medical Oncology, Harbin Medical University Cancer Hospital Harbin 150081, Heilongjiang Province, P. R. China. LA - eng PT - Journal Article DEP - 20211015 PL - United States TA - Am J Cancer Res JT - American journal of cancer research JID - 101549944 PMC - PMC8569365 OTO - NOTNLM OT - LncRNA NR2F2-AS1 OT - MiR-545-5p OT - Non-small cell lung cancer OT - biliverdin reductase OT - c-Met OT - epithelial-mesenchymal transition COIS- None. EDAT- 2021/11/13 06:00 MHDA- 2021/11/13 06:01 PMCR- 2021/10/15 CRDT- 2021/11/12 07:04 PHST- 2020/11/12 00:00 [received] PHST- 2021/09/09 00:00 [accepted] PHST- 2021/11/12 07:04 [entrez] PHST- 2021/11/13 06:00 [pubmed] PHST- 2021/11/13 06:01 [medline] PHST- 2021/10/15 00:00 [pmc-release] PST - epublish SO - Am J Cancer Res. 2021 Oct 15;11(10):4844-4865. eCollection 2021.