A novel axis of circKIF4A-miR-637-STAT3 promotes brain metastasis in triple-negative breast cancer
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved..
Among patients with triple-negative breast cancer (TNBC), distant metastasis is the leading cause of death. Our previous studies have shown that TNBC progression is greatly facilitated by circKIF4A, but uncertainty remains regarding its role in TNBC brain metastasis and the molecular mechanism. In this study, we found notable upregulation of circKIF4A in TNBC cell lines and brain metastases. Inhibition of circKIF4A impaired the ability of TNBC to proliferate, migrate, and cause brain metastasis. Luciferase reporter assays confirmed that circKIF4A competed for binding to miR-637 with STAT3 3' UTR. Western blot analysis revealed that inhibition of circKIF4A decreased STAT3 and p62 expression, while increased the LC3B-II/LC3B-I ratio and the expression of Beclin, indicating that downregulation of circKIF4A induced autophagy by competing with STAT3 for binding to miR-637. By employing a competitive endogenous RNA (ceRNA) mechanism, the circKIF4A-miR-637-STAT3 axis coordinates brain metastasis in TNBC. circKIF4A can therefore be used as a prognostic biomarker for brain metastasis in TNBC and as a therapeutic target.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:581 |
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| Enthalten in: |
Cancer letters - 581(2024) vom: 28. Jan., Seite 216508 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Song [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.12.2023 Date Revised 23.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.canlet.2023.216508 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Wu, Song |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A novel axis of circKIF4A-miR-637-STAT3 promotes brain metastasis in triple-negative breast cancer |
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| 500 | |a published: Print-Electronic | ||
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| 520 | |a Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a Among patients with triple-negative breast cancer (TNBC), distant metastasis is the leading cause of death. Our previous studies have shown that TNBC progression is greatly facilitated by circKIF4A, but uncertainty remains regarding its role in TNBC brain metastasis and the molecular mechanism. In this study, we found notable upregulation of circKIF4A in TNBC cell lines and brain metastases. Inhibition of circKIF4A impaired the ability of TNBC to proliferate, migrate, and cause brain metastasis. Luciferase reporter assays confirmed that circKIF4A competed for binding to miR-637 with STAT3 3' UTR. Western blot analysis revealed that inhibition of circKIF4A decreased STAT3 and p62 expression, while increased the LC3B-II/LC3B-I ratio and the expression of Beclin, indicating that downregulation of circKIF4A induced autophagy by competing with STAT3 for binding to miR-637. By employing a competitive endogenous RNA (ceRNA) mechanism, the circKIF4A-miR-637-STAT3 axis coordinates brain metastasis in TNBC. circKIF4A can therefore be used as a prognostic biomarker for brain metastasis in TNBC and as a therapeutic target | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Autophagy | |
| 650 | 4 | |a Circular RNAs | |
| 650 | 4 | |a Competitive endogenous RNAs | |
| 650 | 4 | |a Triple-negative breast cancer | |
| 650 | 4 | |a circKIF4A | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 650 | 7 | |a STAT3 protein, human |2 NLM | |
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| 700 | 1 | |a Lu, Jibu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Hongbo |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Feiyue |e verfasserin |4 aut | |
| 700 | 1 | |a Mo, Yunxian |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Liming |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Cailu |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Lingrui |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Xiaoming |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yuehua |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Huan |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Hailin |e verfasserin |4 aut | |
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