PMID- 36194200 OWN - NLM STAT- MEDLINE DCOM- 20221215 LR - 20221222 IS - 2410-8650 (Electronic) IS - 1607-551X (Linking) VI - 38 IP - 12 DP - 2022 Dec TI - 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. PG - 1190-1202 LID - 10.1002/kjm2.12602 [doi] AB - 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. CI - (c) 2022 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University. FAU - Lu, Zhi-Hui AU - Lu ZH AD - Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China. FAU - Tu, Gan-Jie AU - Tu GJ AD - Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China. FAU - Fu, Si-Lv AU - Fu SL AD - Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China. FAU - Shang, Kai AU - Shang K AD - Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China. FAU - Peng, Su-Juan AU - Peng SJ AD - Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China. FAU - Chen, Li AU - Chen L AUID- ORCID: 0000-0002-0880-9926 AD - Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China. FAU - Gu, Xi-Juan AU - Gu XJ AD - Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China. LA - eng PT - Journal Article DEP - 20221004 PL - China (Republic : 1949- ) TA - Kaohsiung J Med Sci JT - The Kaohsiung journal of medical sciences JID - 100960562 RN - 0 (B7-H1 Antigen) RN - 0 (NLR Proteins) RN - 0 (Programmed Cell Death 1 Receptor) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (HLA Antigens) RN - 0 (BMI1 protein, human) RN - EC 2.3.2.27 (Polycomb Repressive Complex 1) RN - 0 (NLRC5 protein, human) SB - IM MH - Humans MH - *Carcinoma, Non-Small-Cell Lung/genetics MH - B7-H1 Antigen/metabolism MH - CD8-Positive T-Lymphocytes MH - Proteolysis MH - NLR Proteins/metabolism MH - Caspase Activation and Recruitment Domain MH - Programmed Cell Death 1 Receptor/metabolism MH - Intracellular Signaling Peptides and Proteins/metabolism MH - *Lung Neoplasms/genetics MH - Histocompatibility Antigens Class I/genetics/metabolism MH - Ubiquitination MH - HLA Antigens MH - Polycomb Repressive Complex 1/genetics/metabolism OTO - NOTNLM OT - BMI1 OT - HLA class I OT - NLRC5 OT - PD-1/PD-L1 OT - T cells EDAT- 2022/10/05 06:00 MHDA- 2022/12/16 06:00 CRDT- 2022/10/04 10:53 PHST- 2022/07/22 00:00 [revised] PHST- 2022/05/09 00:00 [received] PHST- 2022/08/29 00:00 [accepted] PHST- 2022/10/05 06:00 [pubmed] PHST- 2022/12/16 06:00 [medline] PHST- 2022/10/04 10:53 [entrez] AID - 10.1002/kjm2.12602 [doi] PST - ppublish SO - Kaohsiung J Med Sci. 2022 Dec;38(12):1190-1202. doi: 10.1002/kjm2.12602. Epub 2022 Oct 4.