Effects of methyl methanesulfonate and UV sensitive gene clone 81 on hepatocellular carcinoma cells / 中华肝胆外科杂志

ABSTRACT

Objective:To detect the expression of methyl methanesulfonate and UV sensitive gene clone 81 (Mus81) in hepatocellular carcinoma(HCC) and to observe the effects of Mus81 on the migration, invasion and metastatic ability of human HCC cells.Methods:Thirty-two tissue specimens were selected from HCC tissues and corresponding paraneoplastic tissues of patients with HCC who underwent surgical resection in Guangzhou Red Cross Hospital Affiliated to Jinan University from January 2020 to June 2021. The expression levels of Mus81 in 32 HCC specimens, 374 HCC samples from the cancer genome atlas database, human normal liver cell line HL-7702 and human HCC cell lines JHH-7, Huh-7 and Hep3B were analyzed. Mus81 knockdown in JHH-7, Huh-7 and overexpressed in Hep3B HCC cell lines were constructed, and the effects of Mus81 on HCC cells were observed by scratch assay, Transwell migration and invasion assay and tail vein injection transfer assay in nude mice.Results:The expression of Mus81 was higher in HCC tissues or cell lines than which in paraneoplastic tissues or normal hepatocyte lines (all P<0.05). The migration rate, metastatic and invasive cell numbers of Mus81-knockdown Huh-7 HCC cells were 22.24%±2.16%, 49.04±5.62, 3.81±1.08, the negative control group were 26.89%±1.15%, 86.81±4.79, 19.78±3.30, and the differences between the two groups were statistically significant ( t=4.24, 26.59, 23.92, all P<0.01). The migration rate, metastatic and invasive cell numbers of Mus81-overexpressed Hep3B HCC cells were 80.57%±5.12%, 18.74±8.07, 33.81±8.44, which were significantly higher than those of the empty vector group 64.17%±7.20%, 10.96±5.32, 3.04±1.13, and the differences were statistically significant ( t=4.15, 4.18, 18.78, all P<0.01). Tail vein transfer experiments in nude mice showed that the total fluorescence expression, weight of metastatic tumors, and the metastatic rates in kidney, vertebral column, neck, axilla and subcutis in nude mice injected with Mus81-knockdown JHH-7 cells were significantly lower than those in the control group (all P<0.05). Conclusion:Mus81 gene expression is upregulated in HCC and promotes the migration, invasion and metastatic ability of HCC cells, suggesting that Mus81 may be a potential therapeutic target for HCC.