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

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.