IGF2BP2 promotes glycolysis and hepatocellular carcinoma stemness by stabilizing CDC45 mRNA via m6A modification

A growing number of studies have
shown the prognostic importance of Cell division cycle protein 45 (CDC45) in
hepatocellular carcinoma (HCC). This study aims to investigate the biological
function and mechanism of CDC45 in HCC. The differential expression and prognostic significance of
CDC45 in HCC and normal tissues were analyzed by bioinformatics. CDC45 was
knocked down and the biological effects of CDC45 in HCC <i>in vitro</i> and
<i>in vivo</i> were measured. Subsequently, using RNA m6A colorimetry and Methylated RNA Immunoprecipitation (MeRIP),
the levels of m6A modification of total RNA and CDC45 were evaluated in cells.
RIP was applied to establish that CDC45 and insulin-like growth factor 2
mRNA-binding protein 2 (IGF2BP2) interact. A test using actinomycin D was
performed to gauge the stability of the CDC45 mRNA. Furthermore, the regulatory
role of IGF2BP2 on CDC45 expression in HCC progression was explored by
overexpressing IGF2BP2. High
expression of CDC45 was correlated with poor prognosis in HCC patients.
Knocking down CDC45 inhibited HCC cell proliferation, migration, invasion, EMT,
stemness, and glycolysis, and promoted apoptosis, which was verified through <i>in
vitro</i> experiments. Additionally, IGF2BP2 was highly expressed in HCC cells,
and it was found to interact with CDC45. Knocking down IGF2BP2 resulted in
reduced stability of CDC45 mRNA. Moreover, overexpression of IGF2BP2 promoted
HCC cell proliferation, migration, invasion, EMT, stemness, and glycolysis,
while inhibiting apoptosis, which was reversed by knocking down CDC45. In general, IGF2BP2 promoted HCC glycolysis and stemness by
stabilizing CDC45 mRNA via m6A modification.