Competitive Sequestration of miR-1183 by lncRNA DDX11-AS1 Drives Gliomagenesis through E2F7 Activation.

IF 4.1 4区医学 Q3 ONCOLOGY

Oncology Research Pub Date : 2025-09-26 eCollection Date: 2025-01-01 DOI:10.32604/or.2025.065380

Jianwei Wang, Xinzhi Yang, Lvbiao Lin, Jianbo Yu, Jie Mao

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引用次数: 0

Abstract

Objectives: Glioma, as the most lethal primary brain malignancy with poor prognosis, requires further elucidation on the functional role of long noncoding RNA (lncRNA) DDX11 antisense RNA 1 (DDX11-AS1) in its pathogenesis, despite its established oncogenic functions in other cancers. Therefore, this study sought to characterize the oncogenic role and molecular mechanism of DDX11-AS1 in glioma.

Methods: DDX11-AS1 expression levels were analyzed in clinical surgical glioma specimens and publicly available datasets. The functional roles of DDX11-AS1 on glioma cell proliferation and migration were investigated using in vitro knockdown and overexpression assays. In vivo tumor growth was assessed using orthotopic glioma-bearing mouse models. To elucidate the regulatory axis involving DDX11-AS1, miR-1183, and E2F transcription factor 7 (E2F7), we performed competitive endogenous RNA (ceRNA) analysis and conducted functional rescue experiments via miR-1183 inhibition.

Results: DDX11-AS1 expression was markedly upregulated in clinical glioma specimens. Functionally, DDX11-AS1 knockdown significantly suppressed glioma cell proliferation and migration in vitro, while its overexpression exacerbated these malignant phenotypes. Orthotopic glioma-bearing mouse models confirmed that DDX11-AS1 drives in vivo glioma tumor growth. Mechanistically, DDX11-AS1 functions as a ceRNA by competitively interacting with miR-1183. Critically, inhibition of miR-1183 rescued the suppressive effects of DDX11-AS1 knockdown on glioma tumorigenic phenotypes and restored E2F7 expression levels.

Conclusions: This study demonstrates that lncRNA DDX11-AS1 promotes glioma progression by regulating the miR-1183/E2F7 axis, indicating a potential therapeutic target for glioma.

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lncRNA DDX11-AS1竞争性隔离miR-1183通过E2F7激活驱动胶质瘤发生

目的：脑胶质瘤作为最致命、预后较差的原发性脑恶性肿瘤，尽管长链非编码RNA (lncRNA) DDX11反义RNA 1 （DDX11- as1）在其他肿瘤中具有致癌功能，但其在其发病机制中的功能作用有待进一步阐明。因此，本研究试图表征DDX11-AS1在胶质瘤中的致癌作用及其分子机制。方法：分析DDX11-AS1在临床手术胶质瘤标本和公开数据集中的表达水平。通过体外敲除和过表达实验研究了DDX11-AS1在胶质瘤细胞增殖和迁移中的功能作用。使用原位胶质瘤小鼠模型评估体内肿瘤生长情况。为了阐明涉及DDX11-AS1、miR-1183和E2F转录因子7 （E2F7）的调控轴，我们进行了竞争性内源性RNA （ceRNA）分析，并通过miR-1183抑制进行了功能拯救实验。结果：DDX11-AS1在临床胶质瘤标本中表达明显上调。功能上，DDX11-AS1敲低显著抑制胶质瘤细胞体外增殖和迁移，而其过表达则加剧了这些恶性表型。原位胶质瘤小鼠模型证实DDX11-AS1驱动体内胶质瘤肿瘤生长。在机制上，DDX11-AS1通过与miR-1183竞争性相互作用而发挥ceRNA的功能。关键的是，抑制miR-1183恢复了DDX11-AS1敲低对胶质瘤致瘤表型的抑制作用，并恢复了E2F7的表达水平。结论：本研究表明lncRNA DDX11-AS1通过调控miR-1183/E2F7轴促进胶质瘤进展，提示胶质瘤的潜在治疗靶点。

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

Oncology Research 医学-肿瘤学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.