miR‐148a‐3p silences the CANX/MHC‐I pathway and impairs CD8+T cell‐mediated immune attack in colorectal cancer

Autor: Tao Yang, Shuhua Gao, Linzhi Guo, Guozhen Zhang, Ting Yang, Lijun Yang, Ying Shao, Wei Gao, Yanfeng Xi, Minrong Cheng, Jinxiu Zheng, Dong Zhang
Rok vydání: 2021
Předmět:
Zdroj: The FASEB Journal. 35
ISSN: 1530-6860
0892-6638
Popis: Nonresponse, or acquired resistance to immune checkpoint inhibitors in colorectal cancer (CRC) highlight the importance of finding potential tolerance mechanisms. Low expression of major histocompatibility complex, class I (MHC-I) on the cell surface of the tumor is one of the main mechanisms of tumor escape from T-cell recognition and destruction. In this study, we demonstrated that a high level of calnexin (CANX) in the tumors is positively correlated with the overall survival in colorectal cancer patients. CANX is a chaperone protein involved in the folding and assembly of MHC-I molecules. Using miRNA target prediction databases and luciferase assays, we identified miR-148a-3p as a potential regulator of CANX. Inhibition of miR-148a-3p restores surface levels of MHC-I and significantly enhanced the effects of CD8+ T-cell-mediated immune attack in vitro and in vivo by promoting CANX expression. These results reveal that miR-148a-3p can function as a tumor promotor in CRC by targeting the CANX/MHC-I axis, which provides a rationale for immunotherapy through targeting the miR-148a-3p/CANX/MHC-I pathway in patients with CRC.
Databáze: OpenAIRE
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