miR-221-5p and miR-186-5p are the critical exosomal miRNAs in bladder cancer induced natural killer cells dysfunction

Autor: Ting Huyan, Mengjiao Li, Chaochao Wang, Wenting Chen, Xiaojie Zhou, Xuanshuo Zhang, Suyang Duan, Shan Gao, Qi Li
Rok vydání: 2022
DOI: 10.21203/rs.3.rs-1851016/v1
Popis: Bladder cancer (BC) is the 10th most commonly diagnosed cancer worldwide, its carcinogenesis mechanism has not been fully elucidated. BC is able to induce natural killer (NK) cells dysfunction and escape their immune surveillance. The present study found that exosome plays an important role in BC induced NK cell dysfunction by impairing viability, and inhibit the cytotoxicity of NK cell on target cells. Meanwhile, BC derived exosome inhibited the expression of important functional receptors NKG2D, NKp30, and CD226 on NK cells and the secretion of perforin and granzyme-B. Through high-throughput sequencing, the critical miRNAs with high expression in BC exosomes were identified. Furthermore, after Dual-Luciferase reporter assay and transfection experiment, miR-221-5p and miR-186-5p was confirmed can interfere the stability of mRNAs of DAP10, CD96, and perforin gene in NK cells and may be the potential targets using in the therapeutic application of BC.
Databáze: OpenAIRE