Circular RNA EPB41 expression predicts unfavorable prognoses in NSCLC by regulating miR-486-3p/eIF5A axis-mediated stemness
Abstract 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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-022-02618-7 |
| _version_ | 1811333863032487936 |
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| author | Mingming Jin Xiyu Liu Yue Wu Yuqing Lou Xue Li Gang Huang |
| author_facet | Mingming Jin Xiyu Liu Yue Wu Yuqing Lou Xue Li Gang Huang |
| author_sort | Mingming Jin |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-13T16:59:11Z |
| format | Article |
| id | doaj.art-087ccda4cbda4f77b75344cb0046fe08 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-04-13T16:59:11Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-087ccda4cbda4f77b75344cb0046fe082022-12-22T02:38:43ZengBMCCancer Cell International1475-28672022-06-0122111510.1186/s12935-022-02618-7Circular RNA EPB41 expression predicts unfavorable prognoses in NSCLC by regulating miR-486-3p/eIF5A axis-mediated stemnessMingming Jin0Xiyu Liu1Yue Wu2Yuqing Lou3Xue Li4Gang Huang5Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health SciencesShanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health SciencesShanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health SciencesShanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health SciencesHealth School Attached to Shanghai University of Medicine and Health SciencesShanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health SciencesAbstract 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.https://doi.org/10.1186/s12935-022-02618-7Non-small cell lung cancerCirc-EPB41miR-486-3peIF5ACancer stem cells |
| spellingShingle | Mingming Jin Xiyu Liu Yue Wu Yuqing Lou Xue Li Gang Huang Circular RNA EPB41 expression predicts unfavorable prognoses in NSCLC by regulating miR-486-3p/eIF5A axis-mediated stemness Cancer Cell International Non-small cell lung cancer Circ-EPB41 miR-486-3p eIF5A Cancer stem cells |
| title | Circular RNA EPB41 expression predicts unfavorable prognoses in NSCLC by regulating miR-486-3p/eIF5A axis-mediated stemness |
| title_full | Circular RNA EPB41 expression predicts unfavorable prognoses in NSCLC by regulating miR-486-3p/eIF5A axis-mediated stemness |
| title_fullStr | Circular RNA EPB41 expression predicts unfavorable prognoses in NSCLC by regulating miR-486-3p/eIF5A axis-mediated stemness |
| title_full_unstemmed | Circular RNA EPB41 expression predicts unfavorable prognoses in NSCLC by regulating miR-486-3p/eIF5A axis-mediated stemness |
| title_short | Circular RNA EPB41 expression predicts unfavorable prognoses in NSCLC by regulating miR-486-3p/eIF5A axis-mediated stemness |
| title_sort | circular rna epb41 expression predicts unfavorable prognoses in nsclc by regulating mir 486 3p eif5a axis mediated stemness |
| topic | Non-small cell lung cancer Circ-EPB41 miR-486-3p eIF5A Cancer stem cells |
| url | https://doi.org/10.1186/s12935-022-02618-7 |
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