Importantly, XPO5 phosphorylation by ERK kinase and its cis/trans isomerization by the prolyl isomerase Pin1 impair XPO5's nucleo-to-cytoplasmic transport ability of pre-miRNAs, leading to downregulation of mature miRNAs in hepatocellular carcinoma.
Furthermore, downregulation of Pin1 by shRNA restores XPO5-dependent pre-miRNA export and effective biogenesis of mature miRNAs, leading to both in vitro and in vivo HCC inhibition.
Although we found no direct association between DICER (rs3742330 and rs13078), DROSHA (rs10719 and rs6877842), RAN (rs14035) or XPO5 (rs11077) polymorphisms and HCC risk, we demonstrated that DICER (rs3742330) and RAN (rs14035) were associated with the survival of HCC patients.
This is the first study reporting that polymorphisms related to miRSNPs have prognostic value in hepatocellular carcinoma and identify the A/A genotype of rs11077 SNP site located in XPO5 3'UTR can help to predict worse prognosis in patients.