MGLL Promotes Pancreatic Cancer Progression and Invasion: Potential Therapeutic Inhibition by Melatonin.

Objective: Pancreatic adenocarcinoma (PAAD) is an aggressive and lethal cancer with limited treatment options and poor prognosis. Monoacylglycerol lipase (MGLL), a key enzyme in lipid metabolism, is thought to play a role in tumor progression, but its function in PAAD remains unclear. This study aims to investigate the expression and functional significance of MGLL in pancreatic cancer and evaluate melatonin (MLT) as a potential inhibitor of MGLL.

Methods: Tissue samples from 22 PAAD patients were collected and analyzed by immunohistochemistry to assess MGLL expression. Bioinformatics tools, including GEPIA and the Human Protein Atlas, were used to compare MGLL expression in pancreatic cancer versus normal tissue, and survival analysis was conducted. In vitro assays, including CCK-8, colony formation, wound healing, and Transwell, were performed on PANC-1 cells to explore the effects of MGLL knockdown using siRNA. Western blotting was used to analyze the impact of MGLL on the P-AKT/AKT signaling pathway and MMP-2/9 expression. The effect of MLT on MGLL expression was evaluated using RNA-seq and qRT-PCR.

Results: MGLL was significantly overexpressed in PAAD tissues and was associated with poor patient prognosis. Silencing MGLL in PANC-1 cells reduced cell proliferation, migration, and invasion, likely via the P-AKT/AKT pathway. MLT treatment effectively downregulated MGLL expression, as well as MMP-2 and MMP-9, suggesting that MLT could serve as a potential MGLL inhibitor.

Conclusion: MGLL promotes pancreatic cancer progression through the P-AKT/AKT signaling pathway, and MLT may offer a novel therapeutic strategy by inhibiting MGLL expression. These findings highlight MGLL as a potential therapeutic target for PAAD.