Bioengineered (Jan 2022)

Inhibitory effect of CC chemokine ligand 23 (CCL23)/ transcription factor activating enhancer binding protein 4 (TFAP4) on cell proliferation, invasion and angiogenesis in hepatocellular carcinoma

  • Weiwei Wang,
  • Jianjun Wu,
  • Xulei Dai,
  • Kun Cheng

Journal volume & issue
Vol. 13, no. 1
pp. 1626 – 1636


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Hepatocellular carcinoma (HCC) is a highly vascularized solid tumor with a fast growth rate. According to bioinformatics analysis, CC chemokine ligand 23 (CCL23) has clinical significance for survival and prognosis in HCC. The online databases TCGA and CCLE were used to analyze the expression level of CCL23, and its expression was also measured in HCC cell lines by RT-qPCR and Western blotting. The STRING database and co-immunoprecipitation were employed to evaluate the association between CCL23 and transcription factor activating enhancer binding protein 4 (TFAP4). Overexpression plasmids for CCL23 (Ov-CCL23) and TFAP4 (Ov-TFAP4) were transfected into Huh-7 cells to detect TFAP4 expression. Huh-7 cells injected with OV-negative control (NC)/Ov-CCL23 or OV-NC/Ov-CCL23 plus Ov-TFAP4 were utilized to study the function of CCL23/TFAP4. Cell proliferation, invasion and human umbilical vein endothelial cell tube formation assays were conducted. The database revealed decreased expression of CCL23 in HCC and that it was commonly downregulated in HCC cell lines. TFAP4 expression was negatively correlated with CCL23. The overexpression of CCL23 inhibited the proliferation and invasion of Huh-7 cells, whereas TFAP4 blocked these effects. Similarly, the supernatant of CCL23-upregulated cells exhibited significantly lower tube formation potential, and low vascular endothelial growth factor A (VEGFA), VEGFRs expression compared with those of non-transfected Huh-7 cells, while TFAP4 plasmid co-transfected markedly increased these. Taken together, the present study suggests that CCL23 is expressed at low levels in HCC; it inhibits HCC cell proliferation, invasion and angiogenesis in vitro; and its action is negatively associated with and can be blocked by TFAP4.