Lysophosphatidylcholine acyltransferase 1 altered phospholipid composition and regulated hepatoma progression

Abstract

Background & aims: Several lipid synthesis pathways play important roles in the development and progression of hepatocellular carcinoma (HCC), although the precise molecular mechanisms remain to be elucidated. Here, we show the relationship between HCC progression and alteration of phospholipid composition regulated by lysophosphatidylcholine acyltransferase (LPCAT).

Methods: Molecular lipidomic screening was performed by imaging mass spectrometry (IMS) in 37 resected HCC specimens. RT-PCR and Western blotting were carried out to examine the mRNA and protein levels of LPCATs, which catalyze the conversion of lysophosphatidylcholine (LPC) into phosphatidylcholine (PC) and have substrate specificity for some kinds of fatty acids. We examined the effect of LPCAT1 overexpression or knockdown on cell proliferation, migration, and invasion in HCC cell lines.

Results: IMS revealed the increase of PC species with palmitoleic acid or oleic acid at the sn-2-position and the reduction of LPC with palmitic acid at the sn-1-position in HCC tissues. mRNA and protein of LPCAT1, responsible for LPC to PC conversion, were more abundant in HCCs than in the surrounding parenchyma. In cell line experiments, LPCAT1 overexpression enriched PCs observed in IMS and promoted cell proliferation, migration, and invasion. LPCAT1 knockdown did viceversa.

Conclusions: Enrichment or depletion of some specific PCs, was found in HCC by IMS. Alteration of phospholipid composition in HCC would affect tumor character. LPCAT1 modulates phospholipid composition to create favorable conditions to HCC cells. LPCAT1 is a potent target molecule to inhibit HCC progression.

Keywords: Ca(2+)-independent phospholipase A(2)β; Cancer lipidomics; DPPC; HCC; Hepatocellular carcinoma; IMS; Imaging mass spectrometry; LPC; LPCAT; LPCAT1; MALDI; NAFLD; PAF; PC; PCA; cPLA(2)α; cytosolic phospholipase A(2)α; dipalmitoyl phosphatidylcholine; hepatocellular carcinoma; iPLA(2)β; imaging mass spectrometry; lysophosphatidylcholine; lysophosphatidylcholine acyltransferase; matrix-assisted laser desorption/ionization; non-alcoholic fatty liver disease; phosphatidylcholine; platelet activating factor; principal component analysis.