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...

Full description

Bibliographic Details
Main Authors: Yang Hui, Zhao Hongbo, Ren Zhongkun, Yi Xiaojia, Zhang Qiao, Yang Zhe, Kuang Yingmin, Zhu Yuechun
Format: Article
Language:English
Published: China Science Publishing & Media Ltd. 2021-12-01
Series:Acta Biochimica et Biophysica Sinica
Subjects:
Online Access:https://www.sciengine.com/doi/10.3724/abbs.2021023
_version_ 1797635812825759744
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.
first_indexed 2024-03-11T12:25:40Z
format Article
id doaj.art-6560a61873194830b4f2c74e5bf6142a
institution Directory Open Access Journal
issn 1672-9145
language English
last_indexed 2024-03-11T12:25:40Z
publishDate 2021-12-01
publisher China Science Publishing & Media Ltd.
record_format Article
series Acta Biochimica et Biophysica Sinica
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
work_keys_str_mv AT yanghui overexpressioncpt1areduceslipidaccumulationviapparacd36axistosuppressthecellproliferationinccrcc
AT zhaohongbo overexpressioncpt1areduceslipidaccumulationviapparacd36axistosuppressthecellproliferationinccrcc
AT renzhongkun overexpressioncpt1areduceslipidaccumulationviapparacd36axistosuppressthecellproliferationinccrcc
AT yixiaojia overexpressioncpt1areduceslipidaccumulationviapparacd36axistosuppressthecellproliferationinccrcc
AT zhangqiao overexpressioncpt1areduceslipidaccumulationviapparacd36axistosuppressthecellproliferationinccrcc
AT yangzhe overexpressioncpt1areduceslipidaccumulationviapparacd36axistosuppressthecellproliferationinccrcc
AT kuangyingmin overexpressioncpt1areduceslipidaccumulationviapparacd36axistosuppressthecellproliferationinccrcc
AT zhuyuechun overexpressioncpt1areduceslipidaccumulationviapparacd36axistosuppressthecellproliferationinccrcc