Department of Emergency Intensive Care Unit, Yijishan Hospital, First Affiliated Hospital of Wannan Medical College, Wuhu City, China.
Department of Neurosurgery, Yijishan Hospital, First Affiliated Hospital of Wannan Medical College, Wuhu City, China.
Bioengineered. 2021 Dec;12(2):9301-9312. doi: 10.1080/21655979.2021.2000244.
microRNAs (miRNAs), through their regulation of the expression and activity of numerous proteins, are involved in almost all cellular processes. As a consequence, dysregulation of miRNA expression is closely associated with the development and progression of cancers. Recently, DNA methylation has been shown to play a key role in miRNA expression dysregulation in tumors. miRNA-204-5p commonly acts in the suppression of oncogenes in tumors. In this study, the levels of miRNA-204-5p were found to be down-regulated in the astrocytoma samples. miRNA-204-5p expression was also down-regulated in two astrocytoma cell lines (U87MG and LN382). Examination of online databases showed that the miRNA-204-5p promoter regions exist in CpG islands, which might be subjected to differential methylation. Subsequently, we showed that the miRNA-204-5p promoter region was hypermethylated in the astrocytoma tissue samples and cell lines. Then we found that ezrin expression was down-regulated with an increase in miRNA-204-5p expression in LN382 and U87MG cells after 5-aza-2'-deoxycytidine (5'AZA) treatment compared with control DMSO treatment. In addition, LN382 and U87MG cells treated with 5'AZA exhibited significantly inhibited cell invasion and migration . In a recovery experiment, cell invasion and migration returned to normal levels as miRNA-204-5p and ezrin levels were restored. Overall, our study suggests that miRNA-204-5p acts as a tumor suppressor to influence astrocytoma invasion and migration by targeting ezrin and that miRNA-204-5p expression is downregulated by DNA methylation. This study provides a new potential strategy for astrocytoma treatment.
微小 RNA(miRNAs)通过调节大量蛋白质的表达和活性,参与几乎所有的细胞过程。因此,miRNA 表达失调与癌症的发生和发展密切相关。最近,DNA 甲基化被证明在肿瘤中 miRNA 表达失调中起着关键作用。miRNA-204-5p 通常在肿瘤中抑制癌基因的作用。在本研究中,星形细胞瘤样本中的 miRNA-204-5p 水平发现下调。miRNA-204-5p 的表达也在两种星形细胞瘤细胞系(U87MG 和 LN382)中下调。在线数据库的检查表明,miRNA-204-5p 启动子区域存在于 CpG 岛中,可能会受到差异甲基化的影响。随后,我们发现星形细胞瘤组织样本和细胞系中 miRNA-204-5p 启动子区域发生了高甲基化。然后我们发现,与对照 DMSO 处理相比,在用 5-氮杂-2'-脱氧胞苷(5'AZA)处理 LN382 和 U87MG 细胞后,miRNA-204-5p 表达增加,ezrin 表达下调。此外,与对照 DMSO 处理相比,在用 5'AZA 处理的 LN382 和 U87MG 细胞中,细胞侵袭和迁移明显受到抑制。在恢复实验中,当 miRNA-204-5p 和 ezrin 水平恢复时,细胞侵袭和迁移恢复正常水平。总体而言,我们的研究表明,miRNA-204-5p 通过靶向 ezrin 作为肿瘤抑制因子发挥作用,影响星形细胞瘤的侵袭和迁移,并且 miRNA-204-5p 的表达受到 DNA 甲基化的下调。本研究为星形细胞瘤的治疗提供了一种新的潜在策略。