STAG2 loss-of-function mutation induces PD-L1 expression in U2OS cells
| Autor: | Zhaoqiang Li, Anmin Jin, Zhirui Nie, Jingxian Liu, Yan Zhang, Wenwen Gao, Wei Xue, Yuhe Hou, Xidong Ye |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Mutation Cell growth Cell Cancer General Medicine Biology Cell cycle medicine.disease_cause medicine.disease Transcriptome 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer cell medicine Cancer research Original Article Carcinogenesis |
| Zdroj: | Annals of Translational Medicine. 7:127-127 |
| ISSN: | 2305-5847 2305-5839 |
| DOI: | 10.21037/atm.2019.02.23 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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