Metadherin-PRMT5 complex enhances the metastasis of hepatocellular carcinoma through the WNT-?-catenin signaling pathway.

ABSTRACT: Accumulating data suggest that metadherin (MTDH) may function as an oncogene. Our previous study showed that MTDH promotes hepatocellular carcinoma (HCC) metastasis via the epithelial-mesenchymal transition. In this study, we aim to further elucidate how MTDH promotes HCC metastasis. Using Co-immunoprecipitation (co-IP) and mass spectrometry, we found that MTDH can specifically bind to protein arginine methyltransferase 5 (PRMT5). Further functional assays revealed that PRMT5 overexpression promoted the proliferation and motility of HCC cells and that knockout of PRMT5 impeded the effect of MTDH. The immunohistochemistry assay/tissue microarray results showed that when MTDH was overexpressed in HCC cells, PRMT5 translocated from the nucleus to the cytoplasm, with the subsequent translocation of ?-catenin from the cytoplasm to the nucleus and upregulation of the WNT-?-catenin signaling pathway. Further in vivo experiments suggested that PRMT5 and ?-catenin played a pivotal role in MTDH-mediated HCC metastasis. We therefore concluded that the MTDH-PRMT5 complex promotes HCC metastasis by regulating the WNT-?-catenin signaling pathway.

SUBMITTER: Zhu K 

PROVIDER: S-EPMC7175245 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature