Of the ten miRNAs predicted by the 3'-UTR of HIF-1α mRNA, PPIX treatment increased miR-199a-5p, leading to the inhibition of E2F3 expression which is upregulated in mesenchymal liver tumor. miR-199a-5p levels were downregulated in HCC with E2F3 overexpression.
Moreover, E2F3 protein level was positively associated with HCC metastasis and functional analysis confirmed the positive role of E2F3 in HCC cell invasion.
Moreover, E2F3 overexpression partially attenuated the tumor suppressive effects of miR-144, and the expression of E2F3 was negatively correlated with miR-144 level in HCC tissues.
The differential expression of cell cycle/growth regulator in hepatocellular carcinoma (HCC) showed a stronger tendency toward cell proliferation with more than 1.5-fold up-regulation of Cyclin C, ERK5, ERK6, E2F-3, TFDP-2 and CK4.