Circular RNA circ-ERBB2 Elevates the Warburg Effect and Facilitates Triple-Negative Breast Cancer Growth by the MicroRNA 136-5p/Pyruvate Dehydrogenase Kinase 4 Axis
Triple-negative breast cancer (TNBC) is an aggressive histological subtype of breast cancer. It has been reported that the circular RNA (circRNA) circ-ERBB2 (circBase identifier hsa_circ_0007766) is mainly distributed in the cytoplasm of TNBC cells and promotes the proliferation and invasion of TNBC cells. This study aimed to explore the molecular mechanism of circ-ERBB2 regulating the progression of TNBC. The expression of circ-ERBB2 was detected by quantitative real-time PCR (qRT-PCR). Loss-of-function experiments were performed to investigate the function of circ-ERBB2 in TNBC cells in vitro and in vivo. The regulatory mechanism of circ-ERBB2 was surveyed by bioinformatics analysis and dual-luciferase reporter and RNA immunoprecipitation (RIP) or RNA pulldown assays. We observed that circ-ERBB2 was overexpressed in TNBC, and TNBC patients with high circ-ERBB2 expression levels had a poor prognosis. Functionally, circ-ERBB2 knockdown constrained TNBC growth in vivo, reduced the Warburg effect, accelerated apoptosis, and repressed the proliferation, migration, and invasion of TNBC cells in vitro. Mechanically, circ-ERBB2 sponged microRNA 136-5p (miR-136-5p) to elevate pyruvate dehydrogenase kinase 4 (PDK4) expression. In conclusion, circ-ERBB2 facilitated the Warburg effect and malignancy of TNBC cells by the miR-136-5p/PDK4 pathway, at least in part. This study supports circ-ERBB2 as a prognostic indicator for TNBC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:41 |
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| Enthalten in: |
Molecular and cellular biology - 41(2021), 10 vom: 24. Sept., Seite e0060920 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huang, Yihong [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.10.2021 Date Revised 25.03.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1128/MCB.00609-20 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM329146785 |
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| 100 | 1 | |a Huang, Yihong |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Circular RNA circ-ERBB2 Elevates the Warburg Effect and Facilitates Triple-Negative Breast Cancer Growth by the MicroRNA 136-5p/Pyruvate Dehydrogenase Kinase 4 Axis |
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| 500 | |a Date Revised 25.03.2022 | ||
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Triple-negative breast cancer (TNBC) is an aggressive histological subtype of breast cancer. It has been reported that the circular RNA (circRNA) circ-ERBB2 (circBase identifier hsa_circ_0007766) is mainly distributed in the cytoplasm of TNBC cells and promotes the proliferation and invasion of TNBC cells. This study aimed to explore the molecular mechanism of circ-ERBB2 regulating the progression of TNBC. The expression of circ-ERBB2 was detected by quantitative real-time PCR (qRT-PCR). Loss-of-function experiments were performed to investigate the function of circ-ERBB2 in TNBC cells in vitro and in vivo. The regulatory mechanism of circ-ERBB2 was surveyed by bioinformatics analysis and dual-luciferase reporter and RNA immunoprecipitation (RIP) or RNA pulldown assays. We observed that circ-ERBB2 was overexpressed in TNBC, and TNBC patients with high circ-ERBB2 expression levels had a poor prognosis. Functionally, circ-ERBB2 knockdown constrained TNBC growth in vivo, reduced the Warburg effect, accelerated apoptosis, and repressed the proliferation, migration, and invasion of TNBC cells in vitro. Mechanically, circ-ERBB2 sponged microRNA 136-5p (miR-136-5p) to elevate pyruvate dehydrogenase kinase 4 (PDK4) expression. In conclusion, circ-ERBB2 facilitated the Warburg effect and malignancy of TNBC cells by the miR-136-5p/PDK4 pathway, at least in part. This study supports circ-ERBB2 as a prognostic indicator for TNBC | ||
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| 700 | 1 | |a Ke, Liming |e verfasserin |4 aut | |
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