Histone chaperone VPS72 up-regulates the expression of H2AFZ and synergistically promotes the progression of hepatocellular carcinoma

doi:10.3877/cma.j.issn.2095-3232.2024.02.017

Abstract

Abstract:

Objective

To investigate the mechanism of histone chaperones VPS72 and H2AFZ in regulating the expression levels and promoting the progression of in hepatocellular carcinoma (HCC).

Methods

The liver cancer cell lines SNU398, Hep3B and SNU449 with relatively high expression of VPS72 were infected with Lenti-shNC, Lenti-shVPS72-1 and Lenti-shVPS72-2 lentiviruses. The liver cancer cell lines with stable knockdown of VPS72 were constructed. The knockdown efficiency was validated by qRT-PCR and Western blot at the mRNA and protein levels. The proliferation and migration capabilities of liver cancer cells treated with different interventions were evaluated by CCK-8 assay, colony formation assay, scratch assay and Transwell chamber assay. The regulatory relationship between VPS72 and H2AFZ was verified by rescue experiment. The expression levels of VPS72 and H2AFZ mRNA and proteins of liver cancer cells in different groups were detected by qRT-PCR and Western blot. Experimental data among multiple groups were assessed by analysis of variance (ANOVA).

Results

Liver cancer cell lines SNU398, Hep3B and SNU449 with relatively high expression of VPS72 were infected with Lenti-shNC, Lenti-shVPS72-1 and Lenti-shVPS72-2 lentiviruses, and liver cancer cell lines with stable knockdown of VPS72 were successfully constructed. Lenti-shVPS72-1 and Lenti-shVPS72-2 successfully interfered with the expression of VPS72 compared with Lenti-shNC in the control group. VPS72 knockdown significantly inhibited the expression of H2AFZ, which was validated in all three cell lines. In SNU398 cells, compared with Lenti-shNC in the control group, the red fluorescence of H2A.Z was weakened in the Lenti-shVPS72-2 group, confirming that the subcellular site of H2A.Z was located in the nucleus. Cell proliferation assay and colony formation experiment found that VPS72 knockdown significantly inhibited the proliferation capabilities of Hep3B and SNU449 cells. Cell scratch assay and Transwell chamber assay showed that the migration abilities of Hep3B and SNU449 cells in the Lenti-shVPS72-1 and Lenti-shVPS72-2 groups were significantly suppressed compared with that of Lenti-shNC in the control group. H2AFZ overexpression rescue experiment showed that the inhibited proliferation and migration phenotypes of Hep3B and SNU449 were not completely alleviated, suggesting a potential synergistical role between VPS72 and H2AFZ.

Conclusions

Histone chaperone VPS72 can up-regulate the expression of histone variant H2AZ1 of HCC, and probably plays a synergistical role with H2AFZ in promoting the progression of HCC. VPS72 can be used as an epigenetic therapy target for HCC.

Key words: Carcinoma, hepatocellular, Histone chaperones, Histone variants, VPS72, H2AFZ

Lei Lyu, Xiao Feng, Kaiming He, Chengli Gao, Zhou Yang, Changchang Jia, Binsheng Fu. Histone chaperone VPS72 up-regulates the expression of H2AFZ and synergistically promotes the progression of hepatocellular carcinoma[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2024, 13(02): 220-226.

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