LncRNA HOXA-AS3 drives glioma progression through miR-542-5p-Mediated regulation of HOXA1 and WNT5A signaling

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2025-09-18 DOI:10.1016/j.brainres.2025.149952

Lianxu Cui , Ruiyu He , Haomin Li , Siwei Peng , Meiru Zhang , Zhanchuan Ma , Zaiyu Li

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引用次数: 0

Abstract

Background

Gliomas represent a class of central nervous system (CNS) malignancies with significant clinical challenges. Our previous work demonstrated that pristimerin treatment effectively suppresses glioma cell progression through the modulation of miR-542-5p expression. However, the upstream regulatory mechanisms controlling miR-542-5p in glioma remain poorly understood.

Methods

Using RNA22 v2 bioinformatics tools, we predicted potential lncRNA-miRNA interactions, followed by TCGA database analysis of HOXA-AS3, HOXA1, and WNT5A expression patterns in glioma specimens. The binding of miR-542-5p to HOXA-AS3 and HOXA1 was confirmed by Dual-luciferase reporter gene assay. Functional validation was performed in U373 and U251 cell lines through genetic manipulation, complemented by in vivo tumor xenograft experiments to assess the pathophysiological role of HOXA-AS3.

Results

Clinical data revealed significant upregulation of HOXA-AS3 and HOXA1 in glioma tissues (p < 0.001). Silencing HOXA-AS3 in U373 cells markedly inhibited cellular proliferation (p = 0.0033) and migration capacity (p < 0.001), while enhancing apoptosis rates. These effects were reversible through miR-542-5p overexpression. In vivo studies demonstrated that knockdown of HOXA-AS3 suppressed tumor growth (p < 0.05), concomitant with reduced arginase-1 expression in tumor-associated macrophages (p = 0.0012). Survival analysis established significant correlations between elevated HOXA-AS3 (p < 0.0001), HOXA1 (p < 0.0001), and WNT5A (p = 0.011) expression with poor patient prognosis.

Conclusions

Our results showed that HOXA-AS3 might promote glioma progression via regulating hsa-miR-542-5p/HOXA1 and WNT5A.

Abstract Image

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LncRNA HOXA-AS3通过mir -542-5p介导的HOXA1和WNT5A信号的调控驱动胶质瘤的进展。

背景：神经胶质瘤是一类中枢神经系统（CNS）恶性肿瘤，具有重要的临床挑战。我们之前的工作表明，pritimerin治疗通过调节miR-542-5p的表达有效地抑制胶质瘤细胞的进展。然而，在胶质瘤中控制miR-542-5p的上游调控机制仍然知之甚少。方法：利用RNA22 v2生物信息学工具预测潜在的lncRNA-miRNA相互作用，然后通过TCGA数据库分析胶质瘤标本中HOXA-AS3、HOXA1和WNT5A的表达模式。通过双荧光素酶报告基因检测证实miR-542-5p与HOXA-AS3和hoxa1的结合。通过基因操作在U373和U251细胞系中进行功能验证，并辅以体内肿瘤异种移植实验来评估HOXA-AS3的病理生理作用。结果：临床数据显示，HOXA-AS3和HOXA1在胶质瘤组织中显著上调（p ）。结论：我们的研究结果表明，HOXA-AS3可能通过调节hsa-miR-542-5p/HOXA1和WNT5A促进胶质瘤的进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.