MicroRNA miR-1275 coordinately regulates AEA/LPA signals via targeting FAAH in lipid metabolism reprogramming of gastric cancer

Abstract

Glycerophospholipid signal and fatty acid metabolism are closely related to the occurrence and progression of tumours, and metabolic reprogramming caused by hydrolytic enzymes plays an important role in gastric cancer (GC). Here, we performed whole transcriptome sequencing and combined qRT-PCR to screen out the significantly high expression of fatty acid amide hydrolase (FAAH) in GC tissues, which was further verified in both TCGA and Oncomine databases. Functional tests confirmed that FAAH played an oncogene role in GC, and silencing FAAH could delay tumour growth, inhibit tumour metastasis, and promote cell apoptosis both in vitro and in vivo. FAAH-mediated lipid metabolism reprogramming through coordinated regulation of arachidonoyl ethanolamide (AEA)/lysophosphatidic acid (LPA) signalling and activated the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) axis to promote GC progression. Luciferase reporter assay and immunofluorescence-fluorescence in situ hybridization (IF-FISH) were applied to validate the interactions of miR-1275/FAAH. Overexpression and knockdown of miR-1275 in vitro could indirectly modulate the above lipid signalling by targeting FAAH, thereby affecting GC progression. Our study indicates that deregulated FAAH is a key lipid signal and the miR-1275/FAAH/AEA/LPA axis can serve as a diagnostic biomarker for GC or as a target for therapy development.