BMI1 induces ubiquitination and protein degradation of Nod‐like receptor family CARD domain containing 5 and suppresses human leukocyte antigen class I expression to induce immune escape in non‐small cell lung cancer
Abstract The Nod‐like receptor (NLR) family CARD domain containing 5 (NLRC5) has been reported as an activator of human leukocyte antigen (HLA) class I that is responsible for immune activity in cancer treatment. This work focuses on the role of BMI1 proto‐oncogene (BMI1) in the NLRC5‐HLA class I ax...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-12-01
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| Series: | Kaohsiung Journal of Medical Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/kjm2.12602 |
| Summary: | Abstract The Nod‐like receptor (NLR) family CARD domain containing 5 (NLRC5) has been reported as an activator of human leukocyte antigen (HLA) class I that is responsible for immune activity in cancer treatment. This work focuses on the role of BMI1 proto‐oncogene (BMI1) in the NLRC5‐HLA class I axis and in immune escape in non‐small cell lung cancer (NSCLC). First, immunoblot analysis and/or reverse transcription‐quantitative polymerase chain reaction were performed, which identified decreased NLRC5 and HLA class I levels in NSCLC tissues and cell lines. NSCLCs were co‐cultured with activated CD8+ T cells. Overexpression of NLRC5 in NSCLC cells elevated the expression of HLA class I and increased the activity of T cells and IL‐2 production, and it reduced the PD‐1/PD‐L1 levels. The ubiquitination and immunoprecipitation assays confirmed that BMI1 bound to NLRC5 to induce is ubiquitination and protein degradation. Downregulation of BMI1 in NSCLC cells elevated NLRC5 and HLA class I levels, and consequently promoted T cell activation and decreased PD‐1/PD‐L1 levels in the co‐culture system. However, overexpression of BMI1 in cells led to inverse trends. In summary, this study demonstrates that BMI1 induces ubiquitination and protein degradation of NLRC5 and suppresses HLA class I expression, which potentially helps immune escape in NSCLC. |
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| ISSN: | 1607-551X 2410-8650 |