Programmed Cell Death Ligand 1-Inhibiting MicroRNAs in Hepatocellular Carcinoma: A Systematic Review

The Programmed cell death ligand-1 (PD-L1), an immune checkpoint molecule, is the ligand of Programmed cell death protein 1 (PD-1). They are crucial molecules in maintaining immune homeostasis. PD-L1/PD-1 axis regulates the initiation and maintenance of tolerance and protects tissues from autoimmune responses; however, cancer cells can use the PD-1/PD-1 axis to evade the anti-tumor response of immune cells. Increased PD-L1 expression is directly associated with poor prognosis in hepatocellular carcinoma (HCC). Although immunotherapy with immune checkpoint inhibitors (ICIs) are leading therapy in cancer treatment, using biomarkers to regulate immune checkpoints at the RNA level is considered a promising tool in novel therapeutic approaches. Increasing evidence has reported that miRNAs are critical regulators of tumor development. Hence, we performed a current systematic review to explore PD-L1 inhibiting miRNAs involved in hepatocellular carcinoma. Five databases were systemically searched to obtain the relevant original articles. Consequently, seventeen studies were included in the current systematic review. According to obtained literatures, some microRNAs, namely miR-194-5p, -675-5p, 194-5p, -1, -455-5p, -223-3p, -513, -195, -506, -329-3p, -424, -411-5p, -182-5p, -200, -378a-3p, -570, -200c, and -513a-5p can inhibit PD-L1 expression in HCC cells. These can ultimately reduce tumor proliferation, inhibit tumor migration, stimulate the chemosensitivity of cancer cells, and induce apoptosis in tumor cells. Moreover, the investigated miRNAs were further analyzed using miRNA target prediction online tools to highlight the future direction of their functions in HCC.