AbstractPurposeS100A6 protein (calcyclin), a small calcium-binding protein of the S100 family, is
often upregulated in various types of cancers, including hepatocellular carcinoma
(HCC). The aim of this study was to illustrate the molecular mechanism of S100A6
in regulating the proliferation and migration of HCC cells.MethodsThe expressions of S100A6 in human HCC and adjacent non-tumor liver specimens were
detected using immunoblotting and quantitative PCR (qPCR). The recombinant
glutathione S-transferase (GST)-tagged human S100A6 protein was purified and
identified. After treatment with S100A6, the proliferation of HepG2 cells was
detected by the MTT and colony formation assay, and the migration of HepG2 cells
was investigated by the transwell migration assay; the protein levels of cyclin D1
(CCND1), E-cadherin, and vimentin were also tested by immunoblotting. The effect
of S100A6 on p21 and nuclear factor-κB pathway was verified by performing
the dual luciferase assay. Then, the expression of p21 and its transcription
activator, p53, was examined using immunoblotting and qPCR, the ubiquitination of
which was investigated through co-immunoprecipitation.ResultsIt was found that the level of S100A6 was higher in the HCC tissues than in the
adjacent non-tumor liver specimens. Exogenous overexpression of S100A6 promoted
the proliferation and migration of HepG2 cells. S100A6 was observed to regulate
p21 mRNA and protein expression levels and decrease p53 protein expression level,
not mRNA level, by promoting the ubiquitination of p53 via the
proteasome-dependent degradation pathway.ConclusionOur study indicated that S100A6 overexpression could promote the proliferation and
migration of HCC cells by enhancing p53 ubiquitin-dependent proteasome
degradation, ultimately regulating the p21 expression level.
Fenretinide inhibits the proliferation and migration of human liver cancer HepG2 cells by downregulating the activation of myosin light chain kinase through the p38‑MAPK signaling pathway
