KLF4 suppresses the migration of hepatocellular carcinoma by transcriptionally upregulating monoglyceride lipase

The dysregulation of cellular metabolism, particularly lipid metabolism, is essential for cancer progress. Monoglyceride lipase (MGLL) is an important fatty acid metabolism enzyme, which converts monoacylglycerides to free fatty acids and glycerol. Despite the expression level of MGLL was reported to be downregulated in Hepatocellular carcinoma (HCC), the clinical significances and molecular mechanism of MGLL downregulation remains unknown. In the current study, the clinical significances of MGLL expression were investigated in 95 patients with HCC and the transcription factors of MGLL were identified in HCC cells. We found that MGLL was frequently downregulated in HCC samples, especially in metastatic tumor tissues. Patients with low MGLL expression owned remarkably lower 5 year-overall survival (5-OS). Functionally, we found that MGLL played an important role in HCC cell migration. Overexpression of MGLL suppressed cell migration and depletion of MGLL by shRNA promoted cell migration. Further studies indicated that KLF4 directly bound to the promoter of MGLL and accelerated MGLL expression, which then led to HCC cell migration decrease. Additionally, the expression levels of KLF4 were positive association with MGLL expression in HCC tissues. Collectively, our data suggest that KLF4 is a key regulator of MGLL. The KLF4-MGLL axis plays an essential role in suppressing HCC cell migration.