PPARα regulates tumor cell proliferation and senescence via a novel target gene carnitine palmitoyltransferase 1C

Yixin Chen, Yongtao Wang, Yaoyao Huang, Hang Zeng, Bingfang Hu, Lihuan Guan, Huizhen Zhang, Aiming Yu, Caroline H.Johnson, Frank J.Gonzalez, Min Huang, Huichang Bi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Carnitine palmitoyltransferase 1C (CPT1C), an enzyme located in the outer mitochondria membrane, has a crucial role in fatty acid transport and oxidation. It is also involved in cell proliferation and is a potential driver for cancer cell senescence. However, its upstream regulatory mechanism is unknown. Peroxisome proliferator activated receptor a (PPARα) is a ligandactivated transcription factor that regulates lipid metabolism and tumor progression. The current study aimed to elucidate whether and how PPARa regulates CPT1C and then affects cancer cell proliferation and senescence. Here, for the first time we report that PPARa directly activated CPT1C transcription and CPT1C was a novel target gene of PPARa, as revealed by dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. Moreover, regulation of CPT1C by PPARα was p53-independent. We further confirmed that depletion of PPARa resulted in low CPT1C expression and then inhibited proliferation and induced senescence of MDA-MB-231 and PANC-1 tumor cell lines in a CPT1C-dependent manner, while forced PPARa overexpression promoted cell proliferation and reversed cellular senescence. Taken together, these results indicate that CPT1C is a novel PPARa target gene that regulates cancer cell proliferation and senescence. The PPARa-CPT1C axis may be a new target for the intervention of cancer cellular proliferation and senescence.

Original languageEnglish (US)
Pages (from-to)474-483
Number of pages10
JournalCarcinogenesis
Volume38
Issue number4
DOIs
StatePublished - 2017

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Carnitine O-Palmitoyltransferase
Peroxisome Proliferator-Activated Receptors
Cell Aging
Cell Proliferation
Genes
Neoplasms
Chromatin Immunoprecipitation
Neoplasm Genes
Tumor Cell Line
Luciferases
Lipid Metabolism
Mitochondria
Transcription Factors
Fatty Acids

ASJC Scopus subject areas

  • Cancer Research

Cite this

PPARα regulates tumor cell proliferation and senescence via a novel target gene carnitine palmitoyltransferase 1C. / Chen, Yixin; Wang, Yongtao; Huang, Yaoyao; Zeng, Hang; Hu, Bingfang; Guan, Lihuan; Zhang, Huizhen; Yu, Aiming; H.Johnson, Caroline; J.Gonzalez, Frank; Huang, Min; Bi, Huichang.

In: Carcinogenesis, Vol. 38, No. 4, 2017, p. 474-483.

Research output: Contribution to journalArticle

Chen, Y, Wang, Y, Huang, Y, Zeng, H, Hu, B, Guan, L, Zhang, H, Yu, A, H.Johnson, C, J.Gonzalez, F, Huang, M & Bi, H 2017, 'PPARα regulates tumor cell proliferation and senescence via a novel target gene carnitine palmitoyltransferase 1C', Carcinogenesis, vol. 38, no. 4, pp. 474-483. https://doi.org/10.1093/carcin/bgx023
Chen, Yixin ; Wang, Yongtao ; Huang, Yaoyao ; Zeng, Hang ; Hu, Bingfang ; Guan, Lihuan ; Zhang, Huizhen ; Yu, Aiming ; H.Johnson, Caroline ; J.Gonzalez, Frank ; Huang, Min ; Bi, Huichang. / PPARα regulates tumor cell proliferation and senescence via a novel target gene carnitine palmitoyltransferase 1C. In: Carcinogenesis. 2017 ; Vol. 38, No. 4. pp. 474-483.
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abstract = "Carnitine palmitoyltransferase 1C (CPT1C), an enzyme located in the outer mitochondria membrane, has a crucial role in fatty acid transport and oxidation. It is also involved in cell proliferation and is a potential driver for cancer cell senescence. However, its upstream regulatory mechanism is unknown. Peroxisome proliferator activated receptor a (PPARα) is a ligandactivated transcription factor that regulates lipid metabolism and tumor progression. The current study aimed to elucidate whether and how PPARa regulates CPT1C and then affects cancer cell proliferation and senescence. Here, for the first time we report that PPARa directly activated CPT1C transcription and CPT1C was a novel target gene of PPARa, as revealed by dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. Moreover, regulation of CPT1C by PPARα was p53-independent. We further confirmed that depletion of PPARa resulted in low CPT1C expression and then inhibited proliferation and induced senescence of MDA-MB-231 and PANC-1 tumor cell lines in a CPT1C-dependent manner, while forced PPARa overexpression promoted cell proliferation and reversed cellular senescence. Taken together, these results indicate that CPT1C is a novel PPARa target gene that regulates cancer cell proliferation and senescence. The PPARa-CPT1C axis may be a new target for the intervention of cancer cellular proliferation and senescence.",
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