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miR-143-3p Promotes TSCM Differentiation and Inhibits Progressive T Cell Differentiation via Inhibiting ABL2 and PAG1
Wenkai Shi1, Jieming Hu1, Hongqiong Wang1
1School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Background:
Adoptive cell therapy (ACT), including CAR-T and TCR-T therapies, shows promise for cancer treatment, depending on infused T cell expansion, persistence and activity. We previously characterized four T-cell subsets (TN, TSCM, TCM and TEM) and their miRNA profiles.
Objectives:
This study investigates miR-143-3p's role in T cell differentiation.
Methods:
Using qPCR, we analyzed miR-143-3p expression. Target genes were validated by dual-luciferase assays. Functional assays assessed differentiation markers, proliferation, apoptosis and cytokine secretion.
Results:
miR-143-3p was upregulated in early-differentiated TSCM but downregulated during progression. We confirmed ABL2 and PAG1 as direct targets suppressed by miR-143-3p. Overexpression increased early markers (LEF1, CCR7 and CD62L) while decreasing late markers (EOMES, KLRG1 and CD45RO). It also enhanced proliferation, reduced apoptosis and suppressed cytokine secretion.
Conclusions:
miR-143-3p promotes TSCM differentiation and inhibits progressive differentiation by targeting ABL2/PAG1, suggesting new ACT optimization strategies.
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