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

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...

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Main Authors: Fang Wen, Hongjian Ling, Rui Ran, Xinya Li, Houmei Wang, Qianfen Liu, Min Li, Tinghe Yu
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Translational Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S1936523324003826
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author Fang Wen
Hongjian Ling
Rui Ran
Xinya Li
Houmei Wang
Qianfen Liu
Min Li
Tinghe Yu
author_facet Fang Wen
Hongjian Ling
Rui Ran
Xinya Li
Houmei Wang
Qianfen Liu
Min Li
Tinghe Yu
author_sort Fang Wen
collection DOAJ
description 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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publishDate 2025-02-01
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series Translational Oncology
spelling doaj-art-773dc72e873047e3bcce6c8215255b5a2025-01-22T05:41:30ZengElsevierTranslational Oncology1936-52332025-02-0152102256LPCAT3 regulates the proliferation and metastasis of serous ovarian cancer by modulating arachidonic acidFang Wen0Hongjian Ling1Rui Ran2Xinya Li3Houmei Wang4Qianfen Liu5Min Li6Tinghe Yu7Laboratory of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaLaboratory of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaLaboratory of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaLaboratory of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaLaboratory of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaWomen and Children's Hospital, Chongqing Medical University (Chongqing Health Center for Women and Children), ChinaLaboratory of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China; Corresponding author.Laboratory of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S1936523324003826Ovarian cancerLPCAT3Lipid metabolismArachidonic acidFerroptosis
spellingShingle Fang Wen
Hongjian Ling
Rui Ran
Xinya Li
Houmei Wang
Qianfen Liu
Min Li
Tinghe Yu
LPCAT3 regulates the proliferation and metastasis of serous ovarian cancer by modulating arachidonic acid
Translational Oncology
Ovarian cancer
LPCAT3
Lipid metabolism
Arachidonic acid
Ferroptosis
title LPCAT3 regulates the proliferation and metastasis of serous ovarian cancer by modulating arachidonic acid
title_full LPCAT3 regulates the proliferation and metastasis of serous ovarian cancer by modulating arachidonic acid
title_fullStr LPCAT3 regulates the proliferation and metastasis of serous ovarian cancer by modulating arachidonic acid
title_full_unstemmed LPCAT3 regulates the proliferation and metastasis of serous ovarian cancer by modulating arachidonic acid
title_short LPCAT3 regulates the proliferation and metastasis of serous ovarian cancer by modulating arachidonic acid
title_sort lpcat3 regulates the proliferation and metastasis of serous ovarian cancer by modulating arachidonic acid
topic Ovarian cancer
LPCAT3
Lipid metabolism
Arachidonic acid
Ferroptosis
url http://www.sciencedirect.com/science/article/pii/S1936523324003826
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