DNA methylation-mediated repression of microRNA-410 promotes the growth of human glioma cells and triggers cell apoptosis through its interaction with STAT3

DNA 甲基化介导的 microRNA-410 抑制促进人类神经胶质瘤细胞的生长,并通过其与 STAT3 的相互作用引发细胞凋亡

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作者:Zhang Wenfu #, Luo Bin #, Rao Binchan #, Luo Jingling, Wang Zhenchang, Wan Zhengdi, Yang Lei

Abstract

This study's purpose was to confirm the observed underexpression of miRNA-410 in glioma tissues and several glioma cells by Quantitative RT-PCR. Our findings suggest that epigenetic alterations occurring at the promoter region of miR-410 may be responsible for the reduced expression of miR-410 in glioma. The occurrence of DNA methylation in the miR-410 promoter was verified to be more prevalent through glioma tissues contrasted to adjacent non-tumor brain tissues through the utilization of methylation-specific PCR and CpG bisulfite sequencing sites in the miR-410 promoter region. Accordantly, miR-410 expression in glioma cell lines was observed to be significantly lesser in comparison to that of the human fetal glial cell line. In addition, it was demonstrated through gain- and loss-of-function investigations that miR-410 exerts significant regulation over cell growth, cell cycle development, and glioma cell apoptosis. The findings of the Luciferase reporter assay and western blot analysis indicate that miR-410 has a direct effect on the 3'-UTR of signal transducer and activator of transcription 3 (STAT3), thereby inhibiting its expression within glioma cells. Besides, our clinical investigation indicates a negative association between miR-410 expression and STAT3 within the glioma tissues of humans. In aggregate, the data provided in this investigation indicates that miR-410 is subjected to underexpression via DNA methylation. Furthermore, it has been observed to perform its function as a tumor suppressor in glioma cells through direct targeting of STAT3. The previously mentioned results could potentially have significant implications for the advancement of a new therapeutic approach for treating glioma.

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