Table 2.

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

Gastrointestinal cancer	miRNA targeted PD-L1	Mechanism of action	Effects
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