Table 2 miRNA-mediated regulation of PD-L1, mechanisms of action, and associated effects in gastrointestinal cancers

Colorectal cancer

miR-214

Axis circEIF3K/miR-214/PD-L1; Involvement of cancer-associated fibroblasts (CAFs)

Facilitation of colorectal cancer advancement under hypoxic conditions through cancer-associated fibroblasts

miR-140-3p

Direct targeting of PD-L1; Inactivation of the PI3K/AKT pathway

Alleviation of inhibitory effects in tumor cells

miR-30a-5p

miR-30a-5p/USP22 pathway; Control of PD-L1 ubiquitination

Facilitation of immune evasion

miR-15b-5p

Downregulates PD-L1 expression

Inhibits tumor formation and increases sensitivity to anti-PD-1 treatment

miR-21-5p, miR-200a

Promotes M2-like polarization of TAMs and enhances PD-L1 expression

Decreases T cell activity, enhances tumor growth; potential target for sensitizing CRC to anti-PD-L1 therapy

miR-124

Decreases PD-L1 expression

Inhibits Tregs, reduces cell proliferation, and suppresses tumor growth

miR-548b-5p, miR-548c-5p

Upregulates PD-L1 expression

Promotes tumor growth and metastasis

miR-148a-3p

Downregulates PD-L1 expression

reduces T-cell apoptosis, and decreases PD-L1 levels induced by IFNγ

miR-497

Downregulates PD-L1 expression

Inhibits Tregs, suppresses cell proliferation, migration, and invasion

miR-191-5p, miR-382-3p, miR-200a-3p, miR-200c-3p, miR-138-5p

Suppresses PD-L1 expression

Reduces tumor migration, promotes anti-tumoral immune responses, inhibits tumor growth, decreases cell viability, enhances sensitivity to chemotherapy

Gastric cancer

miR-105-5p

Binding to a specific cis-acting region; Negative correlation with PD-L1 expression

Activation of CD8 + T cells

miR-940

Promotion of STAT5A ubiquitination; Inhibition of PD-L1 expression

Inhibition of aggressive characteristics

miR-429

Direct targeting of PD-L1; Indirect regulation through lncRNA HIF1A-AS2

Inhibition of tumor development

miR-502-5p

Transcriptional and post-transcriptional downregulation of PD-L1

Inhibition of tumor growth and metastasis

miR-21

Upregulation of miR-21; Mitigation of Th17/Treg cell imbalance

Reduction of Th17 cell population; Increase in Treg cell population

miR-375-3p

Axis hsa_circ_0136666/miR-375-3p/PRKDC and axis miR-375-3p/JAK2/STAT3/PD-L1

Upregulation of PRKDC, modulation of immune checkpoint proteins, phosphorylation of PD-L1, immune evasion,

miR-16-5p

Reduction of PD-L1 expression

Induction of T cell immune response, inhibition of tumor formation

miR-744-5p

Regulates PD-L1 expression

Regulation of SLC7A5, immune evasion and resistance to anti-PD-1 treatment

miR-5193, miR-4443, miR-520 h, miR-496

Direct targeting of PD-L1

Reduced PD-L1 expression, enhanced anti-tumor activity of T cells

Pancreatic cancer

miR-382-3p

PSMB8-AS1/miR-382-3p/STAT1/PD-L1 axis; Upregulation of PD-L1 expression

Therapeutic target

miR-194-5p

Negative correlation with PD-L1 expression; Inhibition of migration, invasion, and proliferation

Inhibition of cancer progression; Facilitation of CD8 + T cell infiltration

miR-148a-3p

hsa_circ_0046523/miR-148a-3p/PD-L1 axis; Upregulation of PD-L1 expression

Mediation of immunosuppressive microenvironment

miR-519

Direct targeting of PD-L1

Inhibits cell invasiveness and induces apoptosis under hypoxic conditions

miR-142-5p

Inhibition of PD-L1 expression

Increased CD4 + and CD8 + T lymphocytes, reduced PD-1 + T lymphocytes, increased IFN-γ and TNF-α production

i

Increased PD-L1 expression

Decreased apoptosis, proliferation, invasion, and migration of pancreatic cancer cells

Esophageal cancer

miR-124-3p

Regulation by circ-VIM; Downregulation of PD-L1 expression

Suppression of immune escape and oncogenic activities; Inhibition of tumor growth and metastases

miR-5590-3p

Competitive binding with PD-L1

Promoting growth, expansion, and metastasis of tumor cells, partially reversed by silencing PD-L1