期刊
CELLULAR & MOLECULAR BIOLOGY LETTERS
卷 26, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s11658-021-00266-9
关键词
Glioma; miRNA; miR-29a; p53; MDM2
资金
- National Nature Science Foundation of China [81772673]
- Reserve Talents Training Plan of Jing'an District
miR-29a is closely associated with p53 signaling in gliomas, affecting cell behaviors and tumor grade. Induced by p53, miR-29a inhibits proliferation, migration, and invasion, and promotes apoptosis in glioma cells. It also regulates the p53-miR29a-MDM2 feedback loop, enhancing sensitivity to temozolomide treatment.
Recently, pivotal functions of miRNAs in regulating common tumorigenic processes and manipulating signaling pathways in brain tumors have been recognized; notably, miR-29a is closely associated with p53 signaling, contributing to the development of glioma. However, the molecular mechanism of the interaction between miR-29a and p53 signaling is still to be revealed. Herein, a total of 30 glioma tissues and 10 noncancerous tissues were used to investigate the expression of miR-29a. CCK-8 assay and Transwell assay were applied to identify the effects of miR-29a altered expression on the malignant biological behaviors of glioma cells in vitro, including proliferation, apoptosis, migration and invasion. A dual-luciferase reporter assay was used to further validate the regulatory effect of p53 or miR-29a on miR-29a or MDM2, respectively, at the transcriptional level. The results showed that miR-29a expression negatively correlated with tumor grade of human gliomas; at the same time it inhibited cell proliferation, migration, and invasion and promoted apoptosis of glioma cells in vitro. Mechanistically, miR-29a expression was induced by p53, leading to aberrant expression of MDM2 targeted by miR-29a, and finally imbalanced the activity of the p53-miR29a-MDM2 feedback loop. Moreover, miR-29a regulating p53/MDM2 signaling sensitized the response of glioma cells to temozolomide treatment. Altogether, the study demonstrated a potential molecular mechanism in the tumorigenesis of glioma, while offering a possible target for treating human glioma in the future.
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