Ubiquitin C‐terminal hydrolase L1 promotes expression of programmed cell death‐ligand 1 in non‐small‐cell lung cancer cells

• DOI: 10.1111/cas.14529
• Publication Date: 2020-06-15T15:35:42Z
• Authors: Rudi Mao; Xiao Tan; Ying Xiao; Xinyu Wang; Zhixing Wei; Jianing Wang; Xiaoyan Wang; Huaiyu Zhou; Lining Zhang; Yongyu Shi
• Keywords: 0301 basic medicine; Lung Neoplasms; T-Lymphocytes; Transcription Factor RelA; Original Articles; B7-H1 Antigen; 3. Good health; Gene Expression Regulation, Neoplastic; Immunomodulation; 03 medical and health sciences; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Biomarkers, Tumor; Humans; Proto-Oncogene Proteins c-akt; Ubiquitin Thiolesterase

AbstractProgrammed cell death‐ligand 1 (PD‐L1) expressed on cancer cells can cause immune escape of non‐small‐cell lung cancer (NSCLC). Elucidation of the regulatory mechanisms of the PD‐L1 expression is a prerequisite for establishing new tumor immunotherapy strategies. Ubiquitin C‐terminal hydrolase L1 (UCHL1) is a regulator of cellular signaling transduction that is aberrantly expressed in NSCLC. However, it is not known whether UCHL1 regulates the expression of PD‐L1 in NSCLC cells. In the present study, we found that UCHL1 promotes the expression of PD‐L1 in NSCLC cell lines. In addition, UCHL1 expressed in NSCLC cells inhibited activation of Jurkat cells through upregulation of PD‐L1 expression in in vitro experiments. Moreover, UCHL1 upregulates PD‐L1 expression through facilitating activation of the AKT‐P65 signaling pathway. In conclusion, these results indicated that UCHL1 promoted PD‐L1 expression in NSCLC cells. This finding implied that inhibition of UCHL1 might suppress immune escape of NSCLC through downregulation of PD‐L1 expression in NSCLC cells.