The HCC-derived exosomes with highly express circUHRF1 and circGSE1, which can not only inhibit the secretion of NK cell-derived IFN-γ and TNF-α, degrade miR-449c-5p, and upregulate TIM-3 expression, so as to reduce the number of NK and tumor invasion, induce NK function exhaustion (Zhang et al., 2020), and also regulate the miR-324-5p/TGFBR1/Smad3 axis to induce Tregs expansion, inhibit CD8+ T cells functions, and cause tumor immune escape (Huang et al., 2022). The gene discussed is SMAD3; the disease is neoplasm.