Liver cancer, the second most commonly diagnosed cancer, is associated with high mortality rates.
E2F4
is a member of the E2F transcription factor family. There are limited studies on the role of
E2F4
in hepatocellular carcinoma (HCC). In this study, the expression of
E2F4
in HCC tissue samples and cell lines was analyzed using quantitative real-time polymerase chain reaction.
E2F4
expression positively correlated with tumor size in patients with HCC. Additionally,
E2F4
expression was greater in HCC cells than in normal LO2 cells. Furthermore, overexpression of
E2F4
significantly enhanced the proliferation, migration, and invasion of HCC cells. The results of a luciferase assay revealed that
E2F4
upregulated the expression of
CDCA3
by binding to its promoter region (1863'-ACGCGCGAGAATG-1875') and consequently promoted proliferation and cell cycle progression of HCC cells. Taken together, these results demonstrated that E2F4 might play a vital role in HCC progression and could serve as a potential biomarker for the diagnosis and as a therapeutic target of HCC.
As a new class of endogenous noncoding RNAs, circular RNAs (circRNAs), have been found to influence cell development and function by sponging microRNAs. MicroRNA (miR)-198 is downregulated in various cancers, including hepatocellular carcinoma (HCC). We therefore searched for dysregulated circRNAs that could sponge miR-198 in HCC. By analyzing relevant circRNA databases (circBase, TargetScan and CircInteractome), we found that the miR-198-binding circRNA hsa_circSP3 is upregulated in HCC. CircSP3 expression correlated negatively with miR-198 expression in HCC tissues. Dual luciferase reporter assays indicated that circSP3 bound to miR-198. CircSP3 overexpression in HCC cells induced expression of cyclin-dependent kinase 4, a target gene of miR-198. Silencing circSP3 inhibited HCC cell proliferation and migration by downregulating cyclin-dependent kinase 4, whereas inhibiting miR-198 reversed those effects.
In vivo
experiments confirmed that circSP3 promoted xenograft tumor growth. These data suggest that circSP3 may be a novel biomarker for HCC.
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