DUBR suppresses migration and invasion of human lung adenocarcinoma cells via ZBTB11-mediated inhibition of oxidative phosphorylation
© 2021. The Author(s), under exclusive licence to CPS and SIMM..
Long noncoding RNAs (lncRNAs) are involved in a variety of cancers, but the role of LncRNA DUBR in lung adenocarcinoma (LUAD), the most prevalent form of lung cancer, remains unclear. In this study we investigated the expression of DUBR in LUAD to ascertain its association with the clinical pathology and prognosis of LUAD. Analysis of mRNA expression in The Cancer Genome Atlas (TCGA) LUAD database and in-house LUAD cohort (n = 94) showed that DUBR was significantly downregulated in LUAD, and was associated with poor prognosis. In LUAD cell lines (H1975, A549), overexpression of DUBR significantly suppressed the migration and invasion of the LUAD cells. We demonstrated that c-Myc could bind to the promoter of DUBR, and transcriptionally suppressed its expression. Knockdown of c-Myc almost completely blocked the invasion and migration of LUAD cells, whereas knockdown of DUBR partially rescued c-Myc-knockdown suppressed cell migration and invasion. Furthermore, DUBR overexpression significantly increased the expression of a downstream protein of DUBR, zinc finger, and BTB domain containing 11 (ZBTB11), in H1975 and A549 cells; knockdown of ZBTB11 partially rescued the DUBR-overexpression suppressed cell migration and invasion; knockdown of c-Myc significantly upregulated the expression of ZBTB11 in LUAD cells. Finally, we revealed that DUBR/ZBTB11 axis suppressed oxidative phosphorylation in LUAD cells. In short, we demonstrate that c-Myc/DUBR/ZBTB11 axis suppresses migration and invasion of LUAD by attenuating cell oxidative phosphorylation, which provides new insights into the regulatory mechanism of DUBR.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:43 |
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| Enthalten in: |
Acta pharmacologica Sinica - 43(2022), 1 vom: 23. Jan., Seite 157-166 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nie, Wei [VerfasserIn] |
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| Links: |
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| Themen: |
C-Myc |
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| Anmerkungen: |
Date Completed 18.03.2022 Date Revised 02.01.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41401-021-00624-5 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM32314604X |
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| 245 | 1 | 0 | |a DUBR suppresses migration and invasion of human lung adenocarcinoma cells via ZBTB11-mediated inhibition of oxidative phosphorylation |
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| 500 | |a Date Revised 02.01.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021. The Author(s), under exclusive licence to CPS and SIMM. | ||
| 520 | |a Long noncoding RNAs (lncRNAs) are involved in a variety of cancers, but the role of LncRNA DUBR in lung adenocarcinoma (LUAD), the most prevalent form of lung cancer, remains unclear. In this study we investigated the expression of DUBR in LUAD to ascertain its association with the clinical pathology and prognosis of LUAD. Analysis of mRNA expression in The Cancer Genome Atlas (TCGA) LUAD database and in-house LUAD cohort (n = 94) showed that DUBR was significantly downregulated in LUAD, and was associated with poor prognosis. In LUAD cell lines (H1975, A549), overexpression of DUBR significantly suppressed the migration and invasion of the LUAD cells. We demonstrated that c-Myc could bind to the promoter of DUBR, and transcriptionally suppressed its expression. Knockdown of c-Myc almost completely blocked the invasion and migration of LUAD cells, whereas knockdown of DUBR partially rescued c-Myc-knockdown suppressed cell migration and invasion. Furthermore, DUBR overexpression significantly increased the expression of a downstream protein of DUBR, zinc finger, and BTB domain containing 11 (ZBTB11), in H1975 and A549 cells; knockdown of ZBTB11 partially rescued the DUBR-overexpression suppressed cell migration and invasion; knockdown of c-Myc significantly upregulated the expression of ZBTB11 in LUAD cells. Finally, we revealed that DUBR/ZBTB11 axis suppressed oxidative phosphorylation in LUAD cells. In short, we demonstrate that c-Myc/DUBR/ZBTB11 axis suppresses migration and invasion of LUAD by attenuating cell oxidative phosphorylation, which provides new insights into the regulatory mechanism of DUBR | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a DUBR | |
| 650 | 4 | |a ZBTB11 | |
| 650 | 4 | |a c-Myc | |
| 650 | 4 | |a long noncoding RNAs | |
| 650 | 4 | |a lung adenocarcinoma | |
| 650 | 4 | |a metastasis | |
| 650 | 4 | |a oxidative phosphorylation | |
| 650 | 7 | |a DNA-Binding Proteins |2 NLM | |
| 650 | 7 | |a MYCBP protein, human |2 NLM | |
| 650 | 7 | |a RNA, Long Noncoding |2 NLM | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 700 | 1 | |a Hu, Min-Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qin |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Qian, Fang-Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Le-le |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Chang-Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Shu-Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jing-Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xue-Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Mi-Die |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Bao-Hui |e verfasserin |4 aut | |
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