Journal of gastroenterology and hepatology · 2026
Oncogenic LPCAT1 Accelerates Intrahepatic Cholangiocarcinoma Development Through PI3K/Akt Signaling-Dependent Cell Cycle Regulation.
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Jiang Enlai, Chen Yuwei, Chen Menglin, Zhou Yongjie, Zheng Daofeng, Xu Qing
Аннотация
BACKGROUND: Intrahepatic cholangiocarcinoma (ICC), a primary liver malignancy arising from the intrahepatic bile ducts, represents one of the most aggressive tumors with a dismal prognosis and ranks second only to hepatocellular carcinoma (HCC) in prevalence. Dysregulation of phospholipid metabolism is increasingly being implicated in tumorigenesis, and lysophosphatidylcholine acyltransferase (LPCAT) family members-key regulatory enzymes-play critical roles in various cancers, including HCC. However, their expression profiles and biological functions in ICC remain undefined.
METHODS: Immunochemistry experiments were used to examine the expression of LPCAT1 in ICC tissues. Both in vitro and in vivo functional assays were performed to investigate the functional role of LPCAT1 in regulating cell proliferation, apoptosis, and tumor growth. RNA sequencing and multiplex immunohistochemistry were used to explore the signaling pathways regulated by LPCAT1.
RESULTS: We identified LPCAT1 as the most significantly upregulated LPCAT in both human and murine ICC tissues. Elevated LPCAT1 expression correlated with poor prognosis in ICC patients. Genetic silencing or overexpression of LPCAT1 dramatically altered the proliferation capacity of ICC cells both in vitro and in vivo. Furthermore, liver-specific LPCAT1 knockout mice (LPCAT1LCKO) exhibited significantly attenuated liver tumor burden in a chemically induced model of ICC. Combined immunoblot and RNA sequencing analyses revealed that LPCAT1 upregulates the expression of cell cycle proteins through activation of the PI3K/AKT signaling pathway, thereby promoting cellular proliferation and accelerating ICC progression.
CONCLUSIONS: LPCAT1 upregulates cell cycle proteins through activation of the PI3K/AKT signaling pathway, thereby promoting cellular proliferation and accelerating ICC progression.
METHODS: Immunochemistry experiments were used to examine the expression of LPCAT1 in ICC tissues. Both in vitro and in vivo functional assays were performed to investigate the functional role of LPCAT1 in regulating cell proliferation, apoptosis, and tumor growth. RNA sequencing and multiplex immunohistochemistry were used to explore the signaling pathways regulated by LPCAT1.
RESULTS: We identified LPCAT1 as the most significantly upregulated LPCAT in both human and murine ICC tissues. Elevated LPCAT1 expression correlated with poor prognosis in ICC patients. Genetic silencing or overexpression of LPCAT1 dramatically altered the proliferation capacity of ICC cells both in vitro and in vivo. Furthermore, liver-specific LPCAT1 knockout mice (LPCAT1LCKO) exhibited significantly attenuated liver tumor burden in a chemically induced model of ICC. Combined immunoblot and RNA sequencing analyses revealed that LPCAT1 upregulates the expression of cell cycle proteins through activation of the PI3K/AKT signaling pathway, thereby promoting cellular proliferation and accelerating ICC progression.
CONCLUSIONS: LPCAT1 upregulates cell cycle proteins through activation of the PI3K/AKT signaling pathway, thereby promoting cellular proliferation and accelerating ICC progression.