Effect of miR‑29a‑3p in exosomes on glioma cells by regulating the PI3K/AKT/HIF‑1α pathway

Abstract

Exosomes secreted by glioma cells can carry a number of bioactive molecules. As the most abundant noncoding RNA in exosomes, microRNAs (miRNAs) are involved in signaling between tumor cells in a number of ways. In addition, hypoxia is an important feature of the microenvironment of most tumors. The present study investigated the effect of miR-29a-3p in glioma exosomes on the proliferation and apoptosis levels of U251 glioma cells under hypoxia. Qualitative PCR results showed that the expression level of miR-29a-3p in plasma exosomes of glioma patients was lower than that of normal subjects. By conducting hypoxia experiments in vitro on U251 glioma cells, it was found that the expression level of miR-29a-3p decreased following hypoxia, while overexpression of miR-29a-3p significantly decreased the proliferation of U251 glioma cells and promoted apoptosis by inhibiting the expression of the antiapoptotic marker Bcl-2 and increasing the expression of the proapoptotic marker Bax The potential targets of miR-29a-3p were predicted by online tools and validated by a dual-luciferase gene reporter assay. miR-29a-3p was found to target and regulate PI3K, which in turn inhibited the activity of the PI3K-AKT pathway, thereby reducing the expression of hypoxia inducible factor (HIF)-1α protein. Furthermore, the effects of miR-29a-3p on proliferation and apoptosis in glioma cells in those processes could be reversed by the PI3K-AKT agonist Recilisib. In addition, the inhibitory effect of miR-29a-3p on the PI3K/AKT/HIF-1α regulatory axis could cause a decrease in the expression levels of pyruvate dehydrogenase kinase-1 and pyruvate dehydrogenase kinase-2 and eventually lead to a reduction in glycolysis in U251 glioma cells. Similarly, Recilisib slowed the inhibitory effect of miR-29a-3p on glycolysis and glycolysis-related molecules. The results of this study tentatively confirm that miR-29a-3p carried by exosomes can be used as a novel diagnostic marker and a potential inhibitory molecule for glioma cells, providing a new theoretical and experimental basis for the precise clinical treatment of glioma.

From bench to bedside: The promising value of exosomes in precision medicine for CNS tumors

“…Typically, miRNAs are the most common of these markers. In a study by Lu et al, the level of miR-29a-3p in exosomes from blood plasma was significantly lower in glioma patients compared to healthy individuals, supporting its potential as a biomarker for the disease [ 11 ]. These biomarkers primarily influence glioma progression directly through gene expression or indirectly by activating specific signaling pathways.…”

Connection between Radiation-Regulating Functions of Natural Products and miRNAs Targeting Radiomodulation and Exosome Biogenesis

“…Exosomal miR-194-5p derived from dying pancreatic cancer induced DNA damage response in tumorrepopulating cells to promote tumor repopulation [93], and its exosome target SDC4 was identified (Table 3). Hypoxia downregulated exosomal miR-29a-3p, while the upregulation of miR-29a-3p inhibited proliferation and triggered apoptosis in glioma cells [134], and its exosome target SMPD3 was identified (Table 3). Overexpressing exosomal miR-149-5p suppressed the metastasis and growth of pituitary tumors [135], and its exosome targets VPS4A and CD34 were identified (Table 3).…”

Exosomes‐mediated crosstalk between glioma and immune cells in the tumor microenvironment

“…Tumor‐associated macrophages play a crucial role in tumor growth, invasion, and metastasis. These inflammatory immune cells have two forms of activation, the M1 type and the M2 type 129 . M1 TAMs have antitumor properties and effectively identify and destroy cancer cells through phagocytosis and cytotoxicity 130,131 .…”

“…These inflammatory immune cells have two forms of activation, the M1 type and the M2 type. 129 M1 TAMs have antitumor properties and effectively identify and destroy cancer cells through phagocytosis and cytotoxicity. 130 , 131 They perform key functions, such as secreting toxic intermediates and various inflammatory factors, activating Th1 cells, participating in the Th1 immune response, and having proinflammatory and antitumor effects.…”