Liver X receptor inhibits the growth of hepatocellular carcinoma cells via regulating HULC/miR-134-5p/FOXM1 axis.

In this study, we found that LXR inhibited HCC cell growth by downregulating HULC, and LXRα (but not LXRβ) caused HULC downregulation. Luciferase reporter assays showed that LXR suppressed transcriptional activity of HULC gene promoter, and chromatin immunoprecipitation assays revealed that LXRα (but not LXRβ) bound to HULC promoter region. Furthermore, LXR increased miR-134-5p while decreased FOXM1 by reducing HULC. Additionally, HULC upregulated FOXM1 via sequestrating miR-134-5p, and miR-134-5p downregulated FOXM1 by targeting 3'-UTR of its mRNA. The in vivo experiments showed that LXR repressed the growth of HCC xenografts, and decreased HULC and FOXM1 while increased miR-134-5p in the xenografts. In summary, these findings for the first time demonstrate that LXR inhibits HCC cell growth by modulating HULC/miR-134-5p/FOXM1 axis, suggesting that the pathway LXR/HULC/miR-134-5p/FOXM1 may serve as a novel target for HCC treatment. PMID: 32711110 [PubMed - as supplied by publisher]
Source: Cellular Signalling - Category: Cytology Authors: Tags: Cell Signal Source Type: research