Molecular mechanism of miRNA regulating PD-L1 expression

PD-L1 (programmed death-ligand 1) binding to PD-1 (programmed cell death protein 1) reduces the proliferation of PD-1-positive cells, inhibits their cytokine secretion, and induces apoptosis. miRNA (microRNA) as an important regulator of gene expression, affects the performance of gene function. Similarly, the expression of PD-L1 is also regulated by miRNA. miRNAs usually negatively regulate gene expression, however, is there positive regulation? We reviewed the molecular mechanisms of the positive and negative regulation of PD-L1 expression by miRNAs. miRNAs mainly indirectly and positively regulate PD-L1 expression through the regulation of tumor suppressor genes PTEN (phosphatase and tensin homolog) and LATS2 (large tumor suppressor kinase 2), oncogene YAP1 (Yes1 associated transcriptional regulator), DNA damage response protein Ku80 (80-kilodalton subunit of the Ku heterodimer protein), etc., while negative regulation is mainly achieved by miRNAs directly binding to the 3′-UTR (3′ untranslated region) of PD-L1 mRNA. And this negative regulation can also be reversed by the negative regulation of miRNAs by RNA-binding protein LIN28 (protein lin-28) or circRNAs (circular RNA) such as circ_0000284 and circ-CPA4. The revealing of this mechanism provides more references and strategies for immune checkpoint therapy of tumors.