Deficiency of BCAT2-mediated branched-chain amino acid catabolism promotes colorectal cancer development
Copyright © 2023. Published by Elsevier B.V..
OBJECTIVE: Branched-chain amino acid (BCAA) metabolism is involved in the development of colorectal cancer (CRC); however, the underlying mechanism remains unclear. Therefore, this study investigates the role of BCAA metabolism in CRC progression.
METHODS: Dietary BCAA was administered to both azoxymethane-induced and azoxymethane/dextran sodium sulfate-induced CRC mouse models. The expression of genes related to BCAA metabolism was determined using RNA sequencing. Adjacent tissue samples, obtained from 58 patients with CRC, were subjected to quantitative real-time PCR and immunohistochemical analysis. Moreover, the suppressive role of branched-chain aminotransferase 2 (BCAT2) in cell proliferation, apoptosis, and xenograft mouse models was investigated. Alterations in BCAAs and activation of downstream pathways were also assessed using metabolic analysis and western blotting.
RESULTS: High levels of dietary BCAA intake promoted CRC tumorigenesis in chemical-induced CRC and xenograft mouse models. Both the mRNA and protein levels of BCAT2 were decreased in tumor tissues of patients with CRC compared to those in normal tissues. Proliferation assays and xenograft models confirmed the suppressive role of BCAT2 in CRC progression. Furthermore, the accumulation of BCAAs caused by BCAT2 deficiency facilitated the chronic activation of mTORC1, thereby mediating the oncogenic effect of BCAAs.
CONCLUSION: BCAT2 deficiency promotes CRC progression through inhibition of BCAAs metabolism and chronic activation of mTORC1.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:1870 |
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| Enthalten in: |
Biochimica et biophysica acta. Molecular basis of disease - 1870(2024), 2 vom: 05. Feb., Seite 166941 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kang, Zi-Ran [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.01.2024 Date Revised 27.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbadis.2023.166941 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364182083 |
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| 100 | 1 | |a Kang, Zi-Ran |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Deficiency of BCAT2-mediated branched-chain amino acid catabolism promotes colorectal cancer development |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Completed 01.01.2024 | ||
| 500 | |a Date Revised 27.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023. Published by Elsevier B.V. | ||
| 520 | |a OBJECTIVE: Branched-chain amino acid (BCAA) metabolism is involved in the development of colorectal cancer (CRC); however, the underlying mechanism remains unclear. Therefore, this study investigates the role of BCAA metabolism in CRC progression | ||
| 520 | |a METHODS: Dietary BCAA was administered to both azoxymethane-induced and azoxymethane/dextran sodium sulfate-induced CRC mouse models. The expression of genes related to BCAA metabolism was determined using RNA sequencing. Adjacent tissue samples, obtained from 58 patients with CRC, were subjected to quantitative real-time PCR and immunohistochemical analysis. Moreover, the suppressive role of branched-chain aminotransferase 2 (BCAT2) in cell proliferation, apoptosis, and xenograft mouse models was investigated. Alterations in BCAAs and activation of downstream pathways were also assessed using metabolic analysis and western blotting | ||
| 520 | |a RESULTS: High levels of dietary BCAA intake promoted CRC tumorigenesis in chemical-induced CRC and xenograft mouse models. Both the mRNA and protein levels of BCAT2 were decreased in tumor tissues of patients with CRC compared to those in normal tissues. Proliferation assays and xenograft models confirmed the suppressive role of BCAT2 in CRC progression. Furthermore, the accumulation of BCAAs caused by BCAT2 deficiency facilitated the chronic activation of mTORC1, thereby mediating the oncogenic effect of BCAAs | ||
| 520 | |a CONCLUSION: BCAT2 deficiency promotes CRC progression through inhibition of BCAAs metabolism and chronic activation of mTORC1 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a BCAT2 | |
| 650 | 4 | |a Branched-chain amino acid | |
| 650 | 4 | |a Colorectal cancer | |
| 650 | 4 | |a Diet | |
| 650 | 7 | |a Amino Acids, Branched-Chain |2 NLM | |
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| 650 | 7 | |a EC 2.6.1.- |2 NLM | |
| 650 | 7 | |a Pregnancy Proteins |2 NLM | |
| 650 | 7 | |a Minor Histocompatibility Antigens |2 NLM | |
| 700 | 1 | |a Jiang, Shanshan |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Ji-Xuan |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Yaqi |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Yile |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jinxian |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Haoyan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Ying-Xuan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Huimin |e verfasserin |4 aut | |
| 700 | 1 | |a Fang, Jing-Yuan |e verfasserin |4 aut | |
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