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

• DOI: 10.3892/mmr.2023.12959
• Publication Date: 2023-02-10T13:25:15Z
• Authors: Zeqiang Liu; Zheng Yang; Lu He
• Keywords: 0301 basic medicine; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Apoptosis; Articles; Glioma; Exosomes; 3. Good health; Phosphatidylinositol 3-Kinases; MicroRNAs; 03 medical and health sciences; Cell Line, Tumor; Tumor Microenvironment; Humans; Hypoxia; Proto-Oncogene Proteins c-akt; Cell Proliferation

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.