fig4

Figure 4. Schematic diagram showing a dual mechanism of PD-L1 regulation by a lncRNA TINCR in breast cancer to mediate resistance to cancer immunotherapy. TINCR was shown to increase PD-L1 expression by upregulating the USP20 via a dual mechanism. TINCR is expressed both in the nucleus and cytoplasm of breast cancer cells. In the cytoplasm, TINCR sponges miR-199a-5p and upregulates USP20 mRNA, thus increasing PD-L1 expression by suppressing its ubiquitination. In the nucleus, TINCR recruits DNMT1 to the gene promoter of miR-199-5p and promotes DNA methylation, thereby inhibiting the transcription of miR-199-5p. PD-L1: Programmed cell death ligand 1; lncRNA: long non-coding RNA; TINCR: tissue differentiation-inducing non-protein coding RNA; USP20: ubiquitin-specific protease 20.