The First Affiliated Hospital, Guangxi Medical University of Chinese Medicine, Nanning, Guangxi, China.
Baiyun Hospital of The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510470, China.
Sci Rep. 2024 Jan 18;14(1):1556. doi: 10.1038/s41598-024-51976-x.
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.
本研究旨在通过定量 RT-PCR 证实 miRNA-410 在胶质瘤组织和几种胶质瘤细胞中观察到的表达下调。我们的研究结果表明,miR-410 启动子区发生的表观遗传改变可能导致 miR-410 在胶质瘤中的表达降低。通过利用甲基化特异性 PCR 和 miR-410 启动子区域的 CpG 二硫代硫酸盐测序位点,证实胶质瘤组织中 miR-410 启动子的 DNA 甲基化发生率明显高于相邻的非肿瘤脑组织。相应地,与人类胎儿神经胶质细胞系相比,胶质瘤细胞系中的 miR-410 表达明显减少。此外,通过增益和失活功能研究表明,miR-410 对细胞生长、细胞周期发育和胶质瘤细胞凋亡具有显著的调节作用。荧光素酶报告基因检测和 Western blot 分析的结果表明,miR-410 对信号转导和转录激活因子 3(STAT3)的 3'-UTR 具有直接影响,从而抑制其在胶质瘤细胞中的表达。此外,我们的临床研究表明 miR-410 表达与人类胶质瘤组织中的 STAT3 呈负相关。总的来说,本研究的数据表明 miR-410 通过 DNA 甲基化受到下调。此外,它已被观察到通过直接靶向 STAT3 在胶质瘤细胞中发挥肿瘤抑制作用。上述结果可能对开发治疗胶质瘤的新治疗方法具有重要意义。