Circular RNA drives resistance to anti-PD-1 immunotherapy by regulating the miR-30a-5p/SOX4 axis in non-small cell lung cancer  

作　　者：Jing Wu Meng-Xuan Zhu Ke-Sang Li Ling Peng Peng-Fei Zhang 

机构地区：[1]Department of Medical Oncology,Zhongshan Hospital,Fudan University,Shanghai 200032,China [2]Cancer Center,Zhongshan Hospital,Fudan University,Shanghai 200032,China [3]Department of Hematology and Oncology,Hwa Mei Hospital,University of Chinese Academy of Sciences,Ningbo 315012,Zhejiang,China [4]Department of Pulmonary and Critical Care Medicine,Zhejiang Provincial People’s Hospital,Hangzhou 310014,Zhejiang,China

出　　处：《Cancer Drug Resistance》2022年第2期261-270,共10页癌症耐药（英文）

基　　金：This study was funded by the National Natural Science Foundation of China(82072575);Medical Scientific Research Foundation of Zhejiang Province,China(2019KY176).

摘　　要：Aim:Circular RNAs are widely and abnormally expressed in human cancer cells,and they participate in cancer progression.However,they have rarely been investigated in the immune evasion of non-small cell lung cancer(NSCLC).Here,we elucidated the function and molecular mechanism of hsa_circ_0020714 in promoting the resistance to anti-PD-1 immunotherapy of NSCLC.Methods:The expression of hsa_circ_0020714 were examined by qRT-PCR.In vivo experiments were executed to investigate the biological function of hsa_circ_0020714 in the sensitivity of NSCLC to anti-PD-1 immunotherapy.The qRT-PCR,fluorescence in situ hybridization,RNA pulldown,RNA immunoprecipitation,and western blot were carried out to investigate the potential regulatory mechanisms of hsa_circ_0020714 in NSCLC immune evasion.Results:The expression of hsa_circ_0020714 was upregulated in NSCLC tissues compared to the paired adjacent non-tumor tissues,and an increased expression of hsa_circ_0020714 was significantly associated with a bad prognosis and resistance to anti-PD-1 immunotherapy in patients with NSCLC.Mechanistically,hsa_circ_0020714 functions as an endogenous miR-30a-5p sponge to enhance SOX4 expression,thereby promoting immune evasion and anti-PD-1 resistance in NSCLC patients.Conclusion:Hsa_circ_0020714 induces the immune evasion and resistance to anti-PD-1 immunotherapy of NSCLC via the miR-30a-5p/SOX4 axis,and may be an promising immunotherapeutic target in NSCLC.

关 键 词：NSCLC immune evasion circRNAs PD-1 immunotherapy resistance 

分 类 号：R73[医药卫生—肿瘤]