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长链非编码 RNA RAD51-AS1 通过提高 EIF5A2 的表达促进卵巢癌的发生。

Long non-coding RNA RAD51-AS1 promotes the tumorigenesis of ovarian cancer by elevating EIF5A2 expression.

机构信息

Department of Obstetrics and Gynecology, Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, 330006, Jiangxi, China.

Reproductive Health Department, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, China.

出版信息

J Cancer Res Clin Oncol. 2024 Apr 7;150(4):179. doi: 10.1007/s00432-024-05671-z.

DOI:10.1007/s00432-024-05671-z
PMID:38584230
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10999386/
Abstract

PURPOSE: The present study aims to determine the molecular mechanism mediated by RAD51 antisense RNA 1 (RAD51-AS1) in ovarian cancer (OvCA). METHODS: The data associated with RAD51-AS1 in OvCA were obtained from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. Relative expression of RAD51-AS1 was detected. Determination of cell proliferation, metastasis, and invasion was performed by cell counting, colony formation, would-healing, and transwell invasion assays. Protein levels were detected by western blotting. The molecular mechanism mediated by RAD51-AS1 was predicted by bioinformatics analysis and verified by dual-luciferase reporter assays. Subcutaneous tumorigenesis models were used to confirm the function of RAD51-AS1 in vivo. RESULTS: Data from TCGA and GEO showed that RAD51-AS1 was associated with poor prognosis in OvCA patients and DNA repair, cell cycle, focal adhesion, and apoptosis in SKOV3.ip cells. High levels of RAD51-AS1 were detected in OvCA cells. Overexpressing RAD51-AS1 enhanced the proliferative, invading, and migratory capabilities of OvCA cells in vitro while silencing RAD51-AS1 exhibited the opposite effects. Mechanically, RAD51-AS1 elevated eukaryotic initiation factor 5A2 (EIF5A2) expression as a sponge for microRNA (miR)-140-3p. Finally, the role of RAD51-AS1 was verified by subcutaneous tumorigenesis models. CONCLUSION: RAD51-AS1 promoted OvCA progression by the regulation of the miR-140-3p/EIF5A2 axis, which illustrated the potential therapeutic target for OvCA.

摘要

目的：本研究旨在确定 RAD51 反义 RNA 1（RAD51-AS1）在卵巢癌（OvCA）中介导的分子机制。

方法：从癌症基因组图谱（TCGA）和基因表达综合（GEO）数据库中获得与 OvCA 中 RAD51-AS1 相关的数据。检测 RAD51-AS1 的相对表达。通过细胞计数、集落形成、划痕愈合和 Transwell 侵袭实验检测细胞增殖、转移和侵袭。通过 Western blot 检测蛋白水平。通过生物信息学分析预测 RAD51-AS1 介导的分子机制，并通过双荧光素酶报告基因实验进行验证。使用皮下肿瘤发生模型在体内证实 RAD51-AS1 的功能。

结果：TCGA 和 GEO 的数据表明，RAD51-AS1 与 OvCA 患者的不良预后以及 SKOV3.ip 细胞中的 DNA 修复、细胞周期、焦点黏附和细胞凋亡有关。在 OvCA 细胞中检测到高水平的 RAD51-AS1。过表达 RAD51-AS1 增强了 OvCA 细胞的体外增殖、侵袭和迁移能力，而沉默 RAD51-AS1 则表现出相反的效果。机制上，RAD51-AS1 作为 microRNA（miR）-140-3p 的海绵，升高了真核起始因子 5A2（EIF5A2）的表达。最后，通过皮下肿瘤发生模型验证了 RAD51-AS1 的作用。

结论：RAD51-AS1 通过调节 miR-140-3p/EIF5A2 轴促进 OvCA 进展，为 OvCA 提供了潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ba/10999386/af254313a35f/432_2024_5671_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ba/10999386/05bf539211b2/432_2024_5671_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ba/10999386/9b490974d72f/432_2024_5671_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ba/10999386/60a2d7b955fe/432_2024_5671_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ba/10999386/72f5a8a03d3d/432_2024_5671_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ba/10999386/e0611aed21f4/432_2024_5671_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ba/10999386/af254313a35f/432_2024_5671_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ba/10999386/05bf539211b2/432_2024_5671_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ba/10999386/9b490974d72f/432_2024_5671_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ba/10999386/60a2d7b955fe/432_2024_5671_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ba/10999386/72f5a8a03d3d/432_2024_5671_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ba/10999386/e0611aed21f4/432_2024_5671_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58ba/10999386/af254313a35f/432_2024_5671_Fig6_HTML.jpg

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Long non-coding RNA RAD51-AS1 promotes the tumorigenesis of ovarian cancer by elevating EIF5A2 expression.

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引用本文的文献

[1]
Molecular mechanism and biological pathway of high-expressed RAD51 in regulating cell adhesion and potentially affecting oral squamous cell carcinoma.

Discov Oncol. 2025-7-4

[2]
Latest Update on lncRNA in Epithelial Ovarian Cancer-A Scoping Review.

Cells. 2025-4-7

[3]
Long noncoding RNA SNHG4 promotes glioma progression via regulating miR-367-3p/MYO1B axis in zebrafish xenografts.

Hum Cell. 2025-2-14

本文引用的文献

[1]
lncRNA AC005224.4/miR-140-3p/SNAI2 regulating axis facilitates the invasion and metastasis of ovarian cancer through epithelial-mesenchymal transition.

Chin Med J (Engl). 2023-5-5

[2]
Circular RNA 0001789 sponges miR-140-3p and regulates PAK2 to promote the progression of gastric cancer.

J Transl Med. 2023-2-5

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LncRNA NALT1 promotes colorectal cancer progression via targeting PEG10 by sponging microRNA-574-5p.

Cell Death Dis. 2022-11-16

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LncRNA KCNQ1OT1 promotes the metastasis of ovarian cancer by increasing the methylation of EIF2B5 promoter.

Mol Med. 2022-9-13

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Eukaryotic initiation factor 5A2 mediates hypoxia-induced autophagy and cisplatin resistance.

Cell Death Dis. 2022-8-5

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Chitosan-Gelatin-EGCG Nanoparticle-Meditated LncRNA TMEM44-AS1 Silencing to Activate the P53 Signaling Pathway for the Synergistic Reversal of 5-FU Resistance in Gastric Cancer.

Adv Sci (Weinh). 2022-8

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CircSCAF8 promotes growth and metastasis of prostate cancer through the circSCAF8-miR-140-3p/miR-335-LIF pathway.

Cell Death Dis. 2022-6-2

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Long noncoding RNA TLNC1 promotes the growth and metastasis of liver cancer via inhibition of p53 signaling.

Mol Cancer. 2022-4-27

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Hsa_circRNA_0088036 acts as a ceRNA to promote bladder cancer progression by sponging miR-140-3p.

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