@article{ATM24366,
author = {Zhirui Nie and Wenwen Gao and Yan Zhang and Yuhe Hou and Jingxian Liu and Zhaoqiang Li and Wei Xue and Xidong Ye and Anmin Jin},
title = {STAG2 loss-of-function mutation induces PD-L1 expression in U2OS cells},
journal = {Annals of Translational Medicine},
volume = {7},
number = {7},
year = {2019},
keywords = {},
abstract = {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.},
issn = {2305-5847}, url = {https://atm.amegroups.org/article/view/24366}
}