Exosomal miR-29a-3p derived from bone marrow stromal cells suppresses malignant behavior of NSCLC by regulating DNMT3A/JAK2/STAT3 axis.

MicroRNAs (miRNAs) can be transported to tumor cells through exosomes secreted by bone marrow mesenchymal stem cells (BMSC-Exos) and exert regulatory functions within cells. Here, we aim to investigate the functional mechanism of miR-29a-3p carried by BMSC-Exos in the treatment of NSCLC. Based on the miRNA/mRNA gene expression data in the UCSC dataset (1029 NSCLC and 110 normal samples), bioinformatics analysis predicted the expression levels of miR-29a-3p and DNMT3A in NSCLC samples and their association with prognosis. Exosomes were isolated from BMSCs and characterized. BMSC-Exos with expressed or knocked out miR-29a-3p were treated A549 cells, and their biological effects on cells were evaluated, including proliferation, migration, and apoptosis. Western blotting was employed to explore the involvement of DNMT3A and JAK2/STAT3 signaling pathways. Furthermore, the binding between miR-29a-3p and DNMT3A was verified through dual-luciferase reporter assay. Following transfection with miR-29a-3p mimic and DNMT3A overexpression vectors, their roles in the biological processes of NSCLC were analyzed. In NSCLC, decreased expression of miR-29a-3p or increased expression of DNMT3A was closely associated with poor prognosis. miR-29a-3p can be transferred from BMSCs to A549 cells via exosomes, thereby inhibiting cell proliferation and migration while promoting apoptosis. DNMT3A was identified as a target gene of miR-29a-3p. Mechanistically, miR-29a-3p upregulation led to decreased DNMT3A expression and impaired JAK2/STAT3 signaling pathway. Overall, this study demonstrated that BMSC-derived exosomal miR-29a-3p restrained NSCLC by reducing DNMT3A/JAK2/STAT3 axis. These findings may provide new insights for the development of NSCLC treatment strategies.