PMID- 35725615 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 1475-2867 (Print) IS - 1475-2867 (Electronic) IS - 1475-2867 (Linking) VI - 22 IP - 1 DP - 2022 Jun 20 TI - Circular RNA EPB41 expression predicts unfavorable prognoses in NSCLC by regulating miR-486-3p/eIF5A axis-mediated stemness. PG - 219 LID - 10.1186/s12935-022-02618-7 [doi] LID - 219 AB - Dysregulation of circular RNAs (circRNAs) has recently been found to play an important role in the progression and development of cancers such as non-small cell lung cancer (NSCLC). Yet the functions of many circRNAs in NSCLC remain unclear. In this study, the circRNA expression profiles in NSCLC tumor tissues and adjacent non-tumorous tissues were detected by high-throughput sequencing. Bioinformatics analyses, the dual-luciferase reporter system, fluorescence in situ hybridization (FISH) and miRNA/mRNA high-throughput sequencing were used to identify circ-EPB41 and its downstream target. The subcutaneous tumor/caudal vein transfer mouse model was used for tumor growth and invasion analysis. The results show that the circ-EPB41 was upregulated in NSCLC tissues and cell lines. Increased circ-EPB41 expression in NSCLC was significantly correlated with malignant characteristics, and positive to post-surgical overall survival of NSCLC patients. Reduced circ-EPB41 expression in NSCLC decreased cell proliferation and invasion in both in vitro and in vivo experiments. The miRNA/mRNA high-throughput sequencing suggested that downregulation of circ-EPB41 promoted microRNA (miR)-486-3p and suppressed eukaryotic translation initiation factor 5A (eIF5A) expression. Luciferase reporter experiments confirmed that miR-486-3p/eIF5A were downstream targets of circ-EPB41. In addition, we also found that downregulation of circ-EPB41 suppressed self-renewal and decreased expression of stemness markers SOX2, OCT-4, Nanog and CD133 by sponging miR-486-3p to enhance eIF5A expression. Taken togeter, these data revealed the important role of circ-EPB41 in regulating NSCLC cell invasion and proliferation by modifying miR-486-3p/eIF5A axis-mediated stemness. We believe our study provides a novel perspective regarding the role of circRNAs in NSCLC progression. CI - (c) 2022. The Author(s). FAU - Jin, Mingming AU - Jin M AUID- ORCID: 0000-0003-3574-2410 AD - Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Road, Pudong New Area, Shanghai, 201318, People's Republic of China. AD - Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China. FAU - Liu, Xiyu AU - Liu X AD - Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Road, Pudong New Area, Shanghai, 201318, People's Republic of China. AD - Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China. FAU - Wu, Yue AU - Wu Y AD - Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Road, Pudong New Area, Shanghai, 201318, People's Republic of China. AD - Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China. FAU - Lou, Yuqing AU - Lou Y AD - Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Road, Pudong New Area, Shanghai, 201318, People's Republic of China. AD - Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China. FAU - Li, Xue AU - Li X AD - Health School Attached to Shanghai University of Medicine and Health Sciences, Shanghai, 200237, People's Republic of China. lixue5303@126.com. FAU - Huang, Gang AU - Huang G AD - Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Road, Pudong New Area, Shanghai, 201318, People's Republic of China. huanggang@sumhs.edu.cn. AD - Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China. huanggang@sumhs.edu.cn. LA - eng GR - 81830052/National Natural Science Foundation of China/ GR - 82003142/National Natural Science Foundation of China/ GR - 81530053/National Natural Science Foundation of China/ PT - Journal Article DEP - 20220620 PL - England TA - Cancer Cell Int JT - Cancer cell international JID - 101139795 PMC - PMC9210757 OTO - NOTNLM OT - Cancer stem cells OT - Circ-EPB41 OT - Non-small cell lung cancer OT - eIF5A OT - miR-486-3p COIS- The authors declare that they have no competing interests. EDAT- 2022/06/21 06:00 MHDA- 2022/06/21 06:01 PMCR- 2022/06/20 CRDT- 2022/06/20 23:47 PHST- 2021/09/03 00:00 [received] PHST- 2022/05/20 00:00 [accepted] PHST- 2022/06/20 23:47 [entrez] PHST- 2022/06/21 06:00 [pubmed] PHST- 2022/06/21 06:01 [medline] PHST- 2022/06/20 00:00 [pmc-release] AID - 10.1186/s12935-022-02618-7 [pii] AID - 2618 [pii] AID - 10.1186/s12935-022-02618-7 [doi] PST - epublish SO - Cancer Cell Int. 2022 Jun 20;22(1):219. doi: 10.1186/s12935-022-02618-7.