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SIRT3 promotes the invasion and metastasis of cervical cancer cells by regulating fatty acid synthase

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Abstract

Sirtuin 3 (SIRT3) modulates mitochondria-localized processes and is implicated in the metabolic reprogramming of cancer cells, especially fatty acid (FA) synthesis. However, the relationship between SIRT3 and aberrant lipid synthesis in cervical cancer remains unclear. Here, we investigated the clinical relevance of SIRT3 expression in cervical squamous cell carcinoma (CSCC), cervical intraepithelial neoplasia (CIN), and normal tissues. To analyze the role of SIRT3 in CCSC in vitro, endogenous SIRT3 levels were up- and down-regulated in SiHa and C33a cells, respectively, via lentiviral-based transfection. Levels were quantified using qRT-PCR. Acetylation levels for acetyl-coA carboxylase (ACC1) were measured with the anti-acetyllysine antibody. Knockdown of SIRT3 reduced levels of cellular lipid content in cells. To investigate the role of SIRT3 in cell proliferation, nude mice were xenografted with SIRT3-overexpressing or SIRT3-knockdown CCSC cells. Overall, the results demonstrate that SIRT3 significantly contributed to the reprogramming of FA synthesis in CCSC by up-regulating ACC1 to promote de novo lipogenesis by SIRT3 deacetylation. Moreover, the findings show that the SIRT3-mediated regulation of FA synthesis played a critical role in the proliferation and metastasis of CCSC cells, suggesting that SIRT3 has therapeutic potential in CCSC treatment.

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Abbreviations

CCSC:

Cervical squamous cell carcinoma

CIN:

Cervical intraepithelial neoplasia

SIRT3:

Sirtuin 3

ACC1:

Acetyl-coA carboxylase 1

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Acknowledgements

This work was supported by the State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia Fund (SKL-HIDCA-2017-3), Xinjiang Uygur Autonomous Region University Research Innovation Team Fund (Proj.No.XJEDU2017T006), and Program for Innovative Research Teams (99-11091107202).

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Authors and Affiliations

  1. Department of Pathology, College of Basic Medicine, Medical University of Xinjiang, Ürümqi, People’s Republic of China

    Li Xiu Xu & Ayshamgul Hasim

  2. Clinical Laboratory Center of People’s Hospital, Xinjiang, People’s Republic of China

    Li Jun Hao

  3. Department of Gynecology in the First Affiliated Hospital, Medical University of Xinjiang, Ürümqi, People’s Republic of China

    Jun Qi Ma

  4. Department of Oncology, Cancer Center in the First Affiliated Hospital, Medical University of Xinjiang, Ürümqi, People’s Republic of China

    Jing Kun Liu

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  1. Li Xiu Xu
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Contributions

LXX and A. H. performed most experiments, analyzed the data, wrote the manuscript; LXX, LJH, and JQL participated in the in vivo study; LXX and JQM analyzed the data and revised the manuscript; and A. H. designed the overall study, supervised the experiments, and analyzed the results.

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Correspondence to Ayshamgul Hasim.

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The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

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Xu, L.X., Hao, L.J., Ma, J.Q. et al. SIRT3 promotes the invasion and metastasis of cervical cancer cells by regulating fatty acid synthase. Mol Cell Biochem 464, 11–20 (2020). https://doi.org/10.1007/s11010-019-03644-2

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  • DOI: https://doi.org/10.1007/s11010-019-03644-2

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