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.

中文翻译：

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SIRT3通过调节脂肪酸合酶促进宫颈癌细胞的侵袭和转移。

Sirtuin 3（SIRT3）调节线粒体定位过程，并参与癌细胞的代谢重编程，尤其是脂肪酸（FA）的合成。但是，SIRT3与子宫颈癌中异常脂质合成之间的关系仍不清楚。在这里，我们调查了SIRT3在宫颈鳞状细胞癌（CSCC），宫颈上皮内瘤变（CIN）和正常组织中表达的临床意义。为了分析SIRT3在体外CCSC中的作用，通过基于慢病毒的转染，分别在SiHa和C33a细胞中上调和下调了内源SIRT3水平。使用qRT-PCR对水平进行定量。用抗乙酰赖氨酸抗体测量乙酰辅酶A羧化酶（ACC1）的乙酰化水平。击倒SIRT3降低了细胞中细胞脂质含量的水平。为了研究SIRT3在细胞增殖中的作用，将裸鼠异种移植了SIRT3过表达或SIRT3敲低的CCSC细胞。总体而言，结果表明，SIRT3通过上调ACC1来促进CCSC中FA合成的重编程，从而通过SIRT3脱乙酰化促进从头产生脂肪。此外，研究结果表明，SIRT3介导的FA合成调控在CCSC细胞的增殖和转移中起着关键作用，表明SIRT3在CCSC治疗中具有治疗潜力。