Background: A tumor suppressor protein, stromal antigen 2 (STAG2), has recurrent mutations or loss of expression in many tumors including in bladder cancer, osteosarcoma (OS), and leukemia. However, the mechanism of STAG2 mutations promoting tumorigenesis is still unclear.
Methods: The distribution of STAG2 mutations in cancer was determined through the COSMIC database; we also generated a STAG2 truncating mutation in OS cell line U2OS cells to mimic a common mutation in OS. CCK-8 assay was employed to evaluate the effect of STAG2 on proliferation and chemo-resistance in OS cells. Cell apoptosis and cell cycle assays were used to assess the effect of STAG2 on apoptosis and the cycle of OS cells. A high throughput RNA sequencing (RNA-Seq) strategy using the Illumina Hiseq 2500 platform was applied to characterize the transcriptome profile from STAG2 knockout and STAG2 WT OS cell lines.
Results: We found that STAG2 deficient-cells exhibited reduced cell proliferation and growth; however, they enhanced cell metastasis and invasion, and increased tolerance to chemotherapeutic drugs. We also found that PD-L1, a molecule involved in tumor immune evasion, was up-regulated in the SATG2-lost cells. Expression profile analysis by RNA-seq revealed that there were changes in the expression of many immune-related genes.
Conclusions: Our findings indicated that STAG2 contributes to cell survival and chemo-resistance to cisplatin of OS, suggesting that deletion of STAG2 may promote tumorigenesis by enhancing the immune evasion capacity of cancer cells.
Keywords: PD-L1; Stromal antigen 2 (STAG2); clustered regularly interspaced short palindromic repeated (CRISPR)/Cas9; cohesin; immune evasion; osteosarcoma (OS).