LPCAT3 regulates the proliferation and metastasis of serous ovarian cancer by modulating arachidonic acid

IF 5 2区医学 Q2 Medicine Translational Oncology Pub Date : 2025-02-01 Epub Date: 2024-12-28 DOI:10.1016/j.tranon.2024.102256

Fang Wen , Hongjian Ling , Rui Ran , Xinya Li , Houmei Wang , Qianfen Liu , Min Li , Tinghe Yu

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Abstract

Background

Lysophosphatidylcholine acyltransferase 3 (LPCAT3) promotes ferroptosis through the incorporating polyunsaturated fatty acids into membrane phospholipids, however, its role in serous ovarian cancer remains unclear. Here explored cancer proliferation and metastasis after modulating LPCAP3.

Methods

LPCAT3 protein in ovarian cancer tissues was detected using bioinformatic and immunohistoche mical assays. Cell behaviors were observed after up- or down-regulating LPCAT3. Lipid metabolites were determined, and then the pathway enrichment analysis was performed.

Results

The expression level of LPCAT3 in serous ovarian cancer tissues was lower than that in other types of ovarian cancer, and high expression was associated with a longer survival time. Overexpressing LPCAT3 reduced cell proliferation, migration and invasion via enhancing ferroptosis and decreasing the survival signaling; these behaviors were enhanced in LPCAT3-downknocked cells, where a higher abundance of arachidonic acid was observed followed by up-regulation of the downstream survival signaling. In vivo, up-regulation of LPCAT3 decreased tumor growth, but down-regulation enhanced tumor growth and metastasis.

Conclusions

LPCAT3 modulated metabolism of arachidonic acid, thereby regulating ferroptosis and the survival signaling to determine cancer growth and metastasis.

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LPCAT3通过调节花生四烯酸调节浆液性卵巢癌的增殖和转移。

背景：溶血磷脂酰胆碱酰基转移酶3 （LPCAT3）通过将多不饱和脂肪酸结合到膜磷脂中促进铁死亡，然而，其在浆液性卵巢癌中的作用尚不清楚。本研究探讨了调控LPCAP3后肿瘤的增殖和转移。方法：采用生物信息学和免疫组织化学方法检测卵巢癌组织中LPCAT3蛋白的表达。上调或下调LPCAT3后观察细胞行为。测定脂质代谢物，然后进行途径富集分析。结果：LPCAT3在浆液性卵巢癌组织中的表达水平低于其他类型卵巢癌，且高表达与较长的生存时间相关。过表达LPCAT3通过增强铁下垂和降低存活信号传导抑制细胞增殖、迁移和侵袭；这些行为在lpcat3敲低的细胞中得到增强，其中花生四烯酸的丰度更高，随后下游生存信号上调。在体内，上调LPCAT3抑制肿瘤生长，下调LPCAT3促进肿瘤生长和转移。结论：LPCAT3可调节花生四烯酸代谢，从而调节铁下垂及存活信号，影响肿瘤生长转移。

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.