Genes, Vol. 16, Pages 466: miR-143-3p Promotes TSCM Differentiation and Inhibits Progressive T Cell Differentiation via Inhibiting ABL2 and PAG1

Genes doi: 10.3390/genes16040466

Authors:
Wenkai Shi
Jieming Hu
Hongqiong Wang
Huishan Zhong
Wenfeng Zhang
Jinquan Wang
Hongwei Shao
Han Shen
Huaben Bo
Changli Tao
Fenglin Wu

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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Wenkai Shi www.mdpi.com