Oncogenic RAS Signaling Promotes Tumor Immunoresistance Through CD47 Targeted By MiR-34a In Lung Cancer

The research of immune checkpoint has attracted worldwide attention due to the amazing effect of immunotherapy curing cancer.As one of the important members of immune checkpoint,CD47 also plays an important role in tumor immunity.High expression of CD47 in most cancers contributes to evasion of the host immune system,but the mechanism of exotic expression of CD47 protein in cancer,especially lung cancer,remains unclear.The occurrence of cancer is often related to gene mutation.In lung cancer,KRAS mutation is the most frequent one.Its mutation is characterized by the permanent activation of KRAS,which continuously affects the expression of downstream pathways,which is likely to lead to the abnormal accumulation of a certain protein to some extent.This characteristic is readily associated with abnormally high expression of CD47 protein.Our study found that mutant KRAS did upregulate the expression of CD47 in lung cancer.Interestingly,we found that the expression of CD47 protein was regulated by miR-34a mediated posttranscriptional regulation,and later studies showed that mutant KRAS activated downstream PI3K signaling via phosphorylated STAT3 by regulating miR-34a through CD47.Our study not only enriched the molecular mechanism of exotic high expression of CD47 in lung cancer,but also provided a new idea of molecular basis and targeting for the clinical treatment of patients with mutant KRAS lung cancer.