BAP31-ELAVL1-SPINK6 axis induces loss of cell polarity and promotes metastasis in hepatocellular carcinoma

Tumor metastasis is the main cause of hepatocellular carcinoma (HCC) related death. Loss of cell polarity may lead to weakened cell adhesion, epithelial-mesenchymal transition (EMT), and metastasis of HCC. However, the mechanism involved in HCC cells polarity loss is still less studied. Here, we found that BAP31 expression increased with tumor grade and metastasis. Moreover, BAP31 silencing inhibited invasion and migration and recovered the polarity of HCC cells. RNA-seq identified SPINK6 was a downstream gene of BAP31, and was associated with tumor stage and metastasis in HCC. IP-MS and IF assays showed that BAP31 bound to the RNA binding protein ELAVL1, and promoted its maturation. In addition, RIP, RNA-FISH, RNA stability and luciferase reporter assays confirmed that ELAVL1 could bind to the 3 'UTR region of SPINK6 mRNA to stabilize its expression. Depletion of SPINK6 inhibited the invasion and migration, re-established the cell polarity and suppressed EMT in HCC cells, while overexpression of SPINK6 partially counteracted BAP31/ELAVL1 knockdown caused attenuation of metastasis and recovery of polarity. Finally, <i>in vivo</i> experiments verified that BAP31-ELAVL1-SPINK6 axis induced cell polarity loss and promoted metastasis in HCC. Our study shed new light on the mechanism of cell polarity loss and metastasis in HCC.