MicroRNA-138-5p Suppresses Non-small Cell Lung Cancer Cells by Targeting PD-L1/PD-1 to Regulate Tumor Microenvironment

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Non-small cell lung cancer (NSCLC) presents treatment challenges due to immune evasion.
• MicroRNA-138 (miR-138) is recognized for its tumor-suppressive roles and immune response regulation.
• The precise mechanism of miR-138 in NSCLC remains incompletely understood.

Purpose of the Study:

• To elucidate the role of miR-138-5p in NSCLC progression and immune modulation.
• To investigate miR-138-5p's impact on tumor cell growth, dendritic cell (DC) maturation, and T cell-mediated cytotoxicity.
• To identify miR-138-5p's molecular targets, including PD-L1 and PD-1, in the context of NSCLC and immune cells.

Main Methods:

• Treatment of NSCLC cell lines (A549/3LL) and mouse models (A549-bearing nude mice, 3LL-bearing C57BL/6) with miR-138-5p.
• Analysis of tumor cell proliferation markers (CCND3, CCND20, Ki67, MCM).
• Assessment of DC maturation, T cell activation, and PD-1/PD-L1 expression in tumor tissues and isolated human NSCLC cells and DCs.

Main Results:

• miR-138-5p treatment reduced tumor cell growth and proliferation markers.
• Increased numbers of tumor-infiltrated DCs and enhanced DC-mediated T cell killing of tumor cells were observed.
• miR-138-5p was found to target PD-L1 on tumor cells and directly down-regulate PD-L1 and PD-1 on DCs and T cells, reducing immune tolerance.

Conclusions:

• miR-138-5p effectively inhibits NSCLC tumor growth.
• The mechanism involves the down-regulation of the PD-1/PD-L1 pathway, thereby activating anti-tumor immunity.
• miR-138-5p represents a promising therapeutic target for NSCLC treatment.