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

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. The expression of hsa_circ_0020714 were examined by qRT-PCR. 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 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. 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 antiPD1 resistance in NSCLC patients. 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.