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

Nov 12, 2025Organogenesis

Bone marrow cell particles containing miR-29a-3p may reduce lung cancer growth by affecting the DNMT3A/JAK2/STAT3 pathway

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Abstract

In non-small cell lung cancer (NSCLC), decreased levels of or increased levels of are associated with poor prognosis.

miR-29a-3p can be transported from bone marrow mesenchymal stem cells to A549 cells via .
Increased levels of miR-29a-3p inhibit cell proliferation and migration while promoting apoptosis in NSCLC cells.
DNMT3A was identified as a target gene of miR-29a-3p and is involved in the regulation of the JAK2/STAT3 signaling pathway.
Upregulation of miR-29a-3p leads to decreased expression of DNMT3A and impairment of the JAK2/STAT3 signaling pathway.

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MicroRNAs (miRNAs) can be transported to tumor cells through secreted by bone marrow mesenchymal stem cells (BMSC-Exos) and exert regulatory functions within cells. Here, we aim to investigate the functional mechanism of 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 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.

Key numbers

1029

NSCLC Samples Analyzed

Total number of NSCLC samples from UCSC database.

110

Normal Samples Analyzed

Total number of normal samples used for comparison in the study.

123 nm

Average Diameter of

Size of isolated from bone marrow stromal cells.

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

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