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hsa-miR-181a-5p 通过 MAPK 通路抑制胶质母细胞瘤的发展:一项临床和实验研究。

hsa-miR-181a-5p inhibits glioblastoma development via the MAPK pathway: and study.

机构信息

Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Oncol Res. 2024 Nov 13;32(12):1949-1958. doi: 10.32604/or.2024.051569. eCollection 2024.

Abstract

BACKGROUND

Glioblastoma remains a highly invasive primary brain malignancy with an undesirable prognosis. Growing evidence has shed light on the importance of microRNAs (miRs), as small non-coding RNAs, in tumor development and progression. The present study leverages the and techniques to investigate the significance of hsa-miR-181a-5p and the underlying hsa-miR-181a-5p-meidated signaling pathway in glioblastoma development.

METHODS

Bioinformatic studies were performed on GSE158284, GSE108474 (REMBRANDT study), TCGA-GTEx, CCLE, GeneMANIA, Reactome, WikiPathways, KEGG, miRDB, and microT-CDS to identify the significance of hsa-miR-181a-5p and its underlying target. Afterward, the U373 cell line was selected and transfected with hsa-miR-181a-5p mimics, and the cell viability, clonogenicity, migration, mRNA expression, apoptosis, and cell cycle were studied using the MTT assay, colony formation test, migration assay, qRT-PCR, and flow cytometry respectively.

RESULTS

hsa-miR-181a-5p expression is decreased in glioblastoma samples. The results have shown that hsa-miR-181a-5p could regulate the MAPK pathway by targeting . The experimental assays have shown that hsa-miR-181a-5p decreases the migration of glioblastoma cells, arrests the cell cycle, and increases the apoptosis rate. Besides downregulating and upregulating , hsa-miR-181a-5p downregulates , , , , and expression in U373 cells. The results were consistent with results regarding the regulatory effect of hsa-miR-181a-5p on the MAPK pathway, leading to tumor suppression in glioblastoma.

CONCLUSIONS

hsa-miR-181a-5p inhibits glioblastoma development partially by regulating the signaling factors of the MAPK pathway.

摘要

背景

胶质母细胞瘤仍然是一种具有不良预后的高度侵袭性原发性脑恶性肿瘤。越来越多的证据表明,微小 RNA(miRs)作为小的非编码 RNA,在肿瘤的发生和发展中具有重要作用。本研究利用 和 技术研究 hsa-miR-181a-5p 的意义及其在胶质母细胞瘤发展中的潜在 hsa-miR-181a-5p 介导的信号通路。

方法

在 GSE158284、GSE108474(REMBRANDT 研究)、TCGA-GTEx、CCLE、GeneMANIA、Reactome、WikiPathways、KEGG、miRDB 和 microT-CDS 上进行生物信息学研究,以确定 hsa-miR-181a-5p 的意义及其潜在靶标。随后,选择 U373 细胞系并转染 hsa-miR-181a-5p 模拟物,分别使用 MTT 检测、集落形成试验、迁移试验、qRT-PCR 和流式细胞术研究细胞活力、集落形成能力、迁移能力、mRNA 表达、细胞凋亡和细胞周期。

结果

hsa-miR-181a-5p 在胶质母细胞瘤样本中表达下调。 结果表明,hsa-miR-181a-5p 可以通过靶向 来调节 MAPK 通路。实验结果表明,hsa-miR-181a-5p 降低了胶质母细胞瘤细胞的迁移能力,使细胞周期停滞,并增加了细胞凋亡率。除了下调 和上调 外,hsa-miR-181a-5p 还下调了 U373 细胞中的 、 、 、 、和 表达。 结果与 hsa-miR-181a-5p 对 MAPK 通路的调控作用一致,从而抑制了胶质母细胞瘤的肿瘤发生。

结论

hsa-miR-181a-5p 通过调节 MAPK 通路的信号因子部分抑制胶质母细胞瘤的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa6c/11576920/013ff5a28c01/OncolRes-32-51569-f001.jpg

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