SUV3 knockdown inhibits proliferation, migration, and invasion of hepatocellular carcinoma cells and induces PD-L1 expression

Abstract

Objective: To study the SUV3 gene role during the process of occurrence and advancement of hepatocellular carcinom. Methods: The The differences in SUV3 expression between hepatocellular carcinoma tissues and normal liver tissues were compared by analyzing transcriptome sequencing data from TCGA and GTEx databases. SUV3 knockdown in different hepatocellular carcinoma cells was performed using RNA interference technology. Overexpression vectors were constructed to overexpress SUV3 in different hepatocellular carcinoma cells. The SUV3 regulatory effect was studied on proliferation, migration, and invasion of hepatocellular carcinoma cells. A subcellular fraction isolation approach was used to investigate whether SUV3 knockdown resulted in the release of mitochondrial DNA into the cytoplasm. Quantitative reverse transcription PCR was applied to investigate whether SUV3 knockdown affected PD-L1 expression. The two groups were compared using a two-tailed t-test. Results: The TCGA database analysis revealed that SUV3 expression was higher in hepatocellular carcinoma tissues than in normal liver tissues, and the prognosis of patients with high SUV3 expression in hepatocellular carcinoma tissues was poor. The quantitative RT-PCR results showed that SUV3 expression was higher in hepatocellular carcinoma tissues than that in paracancerous liver tissue. The MTS assay showed that with SUV3 knockdown, the proliferation rate was significantly lower in hepatocellular carcinoma cells than that of the control hepatocellular carcinoma cells (P<0.01). The proliferation rate was significantly higher in SUV3-overexpressed hepatocellular carcinoma cells than that of control hepatocellular carcinoma cells (P<0.01). Cell scratch assay and cell migration and invasion assay showed that SUV3 knockdown inhibited the migration and invasion of hepatocellular carcinoma cells (P<0.01), while SUV3 overexpression promoted the migration and invasion of hepatocellular carcinoma cells (P<0.05). SUV3 Knockdown led to a decrease in the overall level of mtDNA (P<0.01) in accompanied by an increase in mtDNA level in the cytoplasm (P<0.01), indicating that SUV3 knockdown led to mitochondrial DNA leakage into the cytoplasm. SUV3 knockdown resulted in elevated PD-L1 expression (P<0.001), and overexpression of TREX1 in SUV3 knockdown cells decreased mtDNA levels in the cytoplasm and inhibited SUV3 knockdown, resulting in elevated PD-L1 expression, indicating that SUV3 knockdown induced PD-L1 expression by increasing cytoplasmic DNA levels. Conclusions: The SUV3 gene may play an oncogenic function in hepatocellular carcinoma cells.