Overexpression CPT1A reduces lipid accumulation via PPARα/CD36 axis to suppress the cell proliferation in ccRCC
Clear cell renal carcinoma (ccRCC) is histologically defined by its cytoplasmic lipid deposits. Lipid metabolism disorder largely increases the risk of ccRCC. In this study, we aimed to investigate the biological functions and molecular mechanisms of carnitine palmitoyl transferase 1A (CPT1A) in ccR...
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China Science Publishing & Media Ltd.
2021-12-01
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Series: | Acta Biochimica et Biophysica Sinica |
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Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2021023 |
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author | Yang Hui Zhao Hongbo Ren Zhongkun Yi Xiaojia Zhang Qiao Yang Zhe Kuang Yingmin Zhu Yuechun |
author_facet | Yang Hui Zhao Hongbo Ren Zhongkun Yi Xiaojia Zhang Qiao Yang Zhe Kuang Yingmin Zhu Yuechun |
author_sort | Yang Hui |
collection | DOAJ |
description | Clear cell renal carcinoma (ccRCC) is histologically defined by its cytoplasmic lipid deposits. Lipid metabolism disorder largely increases the risk of ccRCC. In this study, we aimed to investigate the biological functions and molecular mechanisms of carnitine palmitoyl transferase 1A (CPT1A) in ccRCC. Our results showed that CPT1A is decreased in ccRCC clinical samples and cell lines compared with that in normal samples. Lentivirus overexpressing CPT1A was used to investigate the neoplastic phenotypes of ccRCC, and the results showed that lipid accumulation and tumor growth are attenuated both in vitro and in vivo. In addition, CPT1A prevents cholesterol uptake and lipid accumulation by increasing the peroxisome proliferator-activated receptor α (PPARα) level through regulation of Class B scavenger receptor type 1 (SRB1) and cluster of differentiation 36 (CD36). Furthermore, PI3K/Akt signaling pathway promotes tumor cell proliferation in ccRCC, which is related to the enhanced expression of CD36. Functionally, weakened CPT1A expression is critical for lipid accumulation to promote ccRCC development. Collectively, our research unveiled a novel function of CPT1A in lipid metabolism via PPARα/CD36 axis, which provides a new theoretical explanation for the pathogenesis of ccRCC. Targeting CPT1A may be a potential therapeutic strategy to treat ccRCC. |
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language | English |
last_indexed | 2024-03-11T12:25:40Z |
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spelling | doaj.art-6560a61873194830b4f2c74e5bf6142a2023-11-06T09:02:47ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452021-12-015422023110.3724/abbs.202102320d259ccOverexpression CPT1A reduces lipid accumulation via PPARα/CD36 axis to suppress the cell proliferation in ccRCCYang Hui0Zhao Hongbo1Ren Zhongkun2Yi Xiaojia3Zhang Qiao4Yang Zhe5Kuang Yingmin6Zhu Yuechun7["Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Kunming 650500, China","Yunnan Key Laboratory of Stem Cell and Regenerative Medicine, Biomedical Engineering Research Center, Kunming Medical University, Kunming 650500, China"]["Yunnan Key Laboratory of Stem Cell and Regenerative Medicine, Biomedical Engineering Research Center, Kunming Medical University, Kunming 650500, China"]["Department of Neurosurgery, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China"]["Department of Pathology, the Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China"]["Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Kunming 650500, China"]["Department of Pathology, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China"]["Department of Organ Transplantation, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China"]["Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Kunming 650500, China"]Clear cell renal carcinoma (ccRCC) is histologically defined by its cytoplasmic lipid deposits. Lipid metabolism disorder largely increases the risk of ccRCC. In this study, we aimed to investigate the biological functions and molecular mechanisms of carnitine palmitoyl transferase 1A (CPT1A) in ccRCC. Our results showed that CPT1A is decreased in ccRCC clinical samples and cell lines compared with that in normal samples. Lentivirus overexpressing CPT1A was used to investigate the neoplastic phenotypes of ccRCC, and the results showed that lipid accumulation and tumor growth are attenuated both in vitro and in vivo. In addition, CPT1A prevents cholesterol uptake and lipid accumulation by increasing the peroxisome proliferator-activated receptor α (PPARα) level through regulation of Class B scavenger receptor type 1 (SRB1) and cluster of differentiation 36 (CD36). Furthermore, PI3K/Akt signaling pathway promotes tumor cell proliferation in ccRCC, which is related to the enhanced expression of CD36. Functionally, weakened CPT1A expression is critical for lipid accumulation to promote ccRCC development. Collectively, our research unveiled a novel function of CPT1A in lipid metabolism via PPARα/CD36 axis, which provides a new theoretical explanation for the pathogenesis of ccRCC. Targeting CPT1A may be a potential therapeutic strategy to treat ccRCC.https://www.sciengine.com/doi/10.3724/abbs.2021023CD36cholesterolCPT1AgrowthPPARαrenal cancer |
spellingShingle | Yang Hui Zhao Hongbo Ren Zhongkun Yi Xiaojia Zhang Qiao Yang Zhe Kuang Yingmin Zhu Yuechun Overexpression CPT1A reduces lipid accumulation via PPARα/CD36 axis to suppress the cell proliferation in ccRCC Acta Biochimica et Biophysica Sinica CD36 cholesterol CPT1A growth PPARα renal cancer |
title | Overexpression CPT1A reduces lipid accumulation via PPARα/CD36 axis to suppress the cell proliferation in ccRCC |
title_full | Overexpression CPT1A reduces lipid accumulation via PPARα/CD36 axis to suppress the cell proliferation in ccRCC |
title_fullStr | Overexpression CPT1A reduces lipid accumulation via PPARα/CD36 axis to suppress the cell proliferation in ccRCC |
title_full_unstemmed | Overexpression CPT1A reduces lipid accumulation via PPARα/CD36 axis to suppress the cell proliferation in ccRCC |
title_short | Overexpression CPT1A reduces lipid accumulation via PPARα/CD36 axis to suppress the cell proliferation in ccRCC |
title_sort | overexpression cpt1a reduces lipid accumulation via pparα cd36 axis to suppress the cell proliferation in ccrcc |
topic | CD36 cholesterol CPT1A growth PPARα renal cancer |
url | https://www.sciengine.com/doi/10.3724/abbs.2021023 |
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