Long Non-Coding RNA TPTEP1 Exerts Tumor Suppressive Functions via Sequestering miR-4295 to Regulate Growth Arrest and DNA Damage-Inducible 45α Expression in Acute Myeloid Leukemia.

IF 2.5 4区医学 Q3 ONCOLOGY

Cancer Management and Research Pub Date : 2025-06-04 eCollection Date: 2025-01-01 DOI:10.2147/CMAR.S486875

Xueni Liu, Yonghui Gui, Chao Wang, Kang Xia, Peng Yang

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引用次数: 0

Abstract

Introduction: Recent evidences show that long non-coding RNA (lncRNA) plays an essential role in physiology and pathophysiology. The purpose of this study was to determine the role and its potential underlying mechanisms of the lncRNA transmembrane phosphatase with tensin homology pseudogene 1 (TPTEP1) in acute myeloid leukemia (AML).

Methods: We detected the TPTEP1 and miR-4295 expression levels in AML cells. The vitro effects of TPTEP1 and miR-4295 on AML cells were analyzed. The correlation between miR-4295 and TPTEP1 or Growth arrest and DNA damage-inducible 45α (GADD45α) was confirmed by a luciferase reporter assay and RNA immunoprecipitation. The expression of GADD45α was investigated by Western blotting.

Results: TPTEP1 was down-regulated in AML cell lines and AML patients. Ectopic expression of TPTEP1 inhibited AML cells proliferation while promoted cells apoptosis. And we found that silencing miR-4295 produced the similar effect of TPTEP1 overexpression. TPTEP1 regulated the malignant behavior of AML cells by binding to miR-4295. In addition, overexpression of TPTEP up-regulated GADD45α, a direct target of miR-4295 which play a suppressive role in AML cells. Moreover, when AML cell lines were treated with a DNA methylation inhibitor, TPTEP1 expression was up-regulated.

Conclusion: This study reveals that the lncRNA TPTEP1 regulates the expression of GADD45α by sponging miR-4295 in AML cells, which may represent a novel therapeutic target for AML.

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长链非编码RNA TPTEP1通过隔离miR-4295调控生长阻滞和DNA损伤诱导的45α在急性髓系白血病中的表达，发挥肿瘤抑制功能。

近年来的研究表明，长链非编码RNA （lncRNA）在生理和病理生理中发挥着重要作用。本研究的目的是确定具有紧张素同源伪基因1的lncRNA跨膜磷酸酶（TPTEP1）在急性髓性白血病（AML）中的作用及其潜在机制。方法：检测AML细胞中TPTEP1和miR-4295的表达水平。分析TPTEP1和miR-4295对AML细胞的体外作用。通过荧光素酶报告基因测定和RNA免疫沉淀证实了miR-4295与TPTEP1或生长阻滞和DNA损伤诱导45α (GADD45α)之间的相关性。Western blotting检测GADD45α的表达。结果：TPTEP1在AML细胞系和AML患者中表达下调。TPTEP1异位表达抑制AML细胞增殖，促进细胞凋亡。我们发现沉默miR-4295会产生与TPTEP1过表达相似的效果。TPTEP1通过结合miR-4295调节AML细胞的恶性行为。此外，过表达TPTEP上调了在AML细胞中发挥抑制作用的miR-4295的直接靶点GADD45α。此外，当用DNA甲基化抑制剂处理AML细胞系时，TPTEP1的表达上调。结论：本研究揭示lncRNA TPTEP1通过海绵化miR-4295调控AML细胞中GADD45α的表达，可能是AML治疗的新靶点。

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

Cancer Management and Research Medicine-Oncology

CiteScore

7.40

自引率

0.00%

发文量

448

审稿时长

16 weeks

期刊介绍： Cancer Management and Research is an international, peer reviewed, open access journal focusing on cancer research and the optimal use of preventative and integrated treatment interventions to achieve improved outcomes, enhanced survival, and quality of life for cancer patients. Specific topics covered in the journal include: ◦Epidemiology, detection and screening ◦Cellular research and biomarkers ◦Identification of biotargets and agents with novel mechanisms of action ◦Optimal clinical use of existing anticancer agents, including combination therapies ◦Radiation and surgery ◦Palliative care ◦Patient adherence, quality of life, satisfaction The journal welcomes submitted papers covering original research, basic science, clinical & epidemiological studies, reviews & evaluations, guidelines, expert opinion and commentary, and case series that shed novel insights on a disease or disease subtype.