AC104024.2/miR-30a-5p Axis Regulates Malignant Progression of Breast Cancer Through a Depression-Related Gene, MAP2K3.

IF 2.5 4区 医学 Q3 CELL BIOLOGY
Jun Li, Jie Sun, Lili Jiang, Xue Bai, Jiyue Gao, Zuowei Zhao
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引用次数: 0

Abstract

Background: Breast cancer (BC), a malignant tumor, is characterized by high incidence and poor prognosis among women worldwide. Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) can regulate the initiation and progression of BC through competitive endogenous RNA (ceRNA) mechanisms. Despite depression being an important factor affecting patients with BC, the ceRNA regulatory network involving depression-related genes in BC remains unclear.

Methods: In this study, we explored the role of the AC104024.2/miR-30a-5p axis in BC progression by targeting the depression-related gene mitogen-activated protein kinase kinase 3 (MAP2K3). We used depression-like mouse models to confirm the role of MAP2K3 in modulating depressive behavior. Additionally, gene set enrichment analyses (GSEA) and phenotypic experiments were conducted to verify the effects of the AC104024.2/miR-30a-5p/MAP2K3 axis on BC cell proliferation, migration, and apoptosis. Luciferase reporter assays were performed to demonstrate the ceRNA function of AC104024.2 for miR-30a-5p.

Results: Our results showed that the AC104024.2/miR-30a-5p axis promotes the malignant progression of BC by regulating MAP2K3. In depression-like mouse models, MAP2K3 was identified as a key gene modulating depressive behavior. The AC104024.2/miR-30a-5p/MAP2K3 axis significantly influenced BC cell proliferation, migration, and apoptosis. Luciferase reporter assays confirmed that AC104024.2 acts as a ceRNA for miR-30a-5p, thereby affecting MAP2K3 expression. Rescue experiments suggested that the regulatory effects of AC104024.2 on BC malignancy are at least partly dependent on MAP2K3.

Conclusion: This study uncovered the role of the depression-related ceRNA network in BC progression and identified AC104024.2 and MAP2K3 as potential biomarkers for the diagnosis and treatment of BC. These findings provide significant clinical implications and applications for the management of BC.

AC104024.2/miR-30a-5p轴通过抑郁相关基因MAP2K3调控乳腺癌恶性进展
背景:乳腺癌(Breast cancer, BC)是一种恶性肿瘤,在全世界女性中发病率高、预后差。长链非编码RNA (lncRNAs)和microRNAs (miRNAs)可以通过竞争性内源性RNA (ceRNA)机制调节BC的起始和进展。尽管抑郁是影响BC患者的重要因素,但在BC中涉及抑郁相关基因的ceRNA调控网络尚不清楚。方法:在本研究中,我们通过靶向抑郁相关基因丝裂原活化蛋白激酶3 (MAP2K3),探索AC104024.2/miR-30a-5p轴在BC进展中的作用。我们使用抑郁样小鼠模型来证实MAP2K3在调节抑郁行为中的作用。此外,通过基因集富集分析(GSEA)和表型实验验证AC104024.2/miR-30a-5p/MAP2K3轴对BC细胞增殖、迁移和凋亡的影响。荧光素酶报告基因检测证实AC104024.2对miR-30a-5p的ceRNA功能。结果:我们的研究结果表明,AC104024.2/miR-30a-5p轴通过调节MAP2K3促进BC的恶性进展。在抑郁样小鼠模型中,MAP2K3被确定为调节抑郁行为的关键基因。AC104024.2/miR-30a-5p/MAP2K3轴显著影响BC细胞增殖、迁移和凋亡。荧光素酶报告基因检测证实AC104024.2作为miR-30a-5p的ceRNA,从而影响MAP2K3的表达。挽救实验表明,AC104024.2对BC恶性肿瘤的调节作用至少部分依赖于MAP2K3。结论:本研究揭示了抑郁相关的ceRNA网络在BC进展中的作用,并确定了AC104024.2和MAP2K3作为BC诊断和治疗的潜在生物标志物。这些发现为BC的治疗提供了重要的临床意义和应用。
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来源期刊
Analytical Cellular Pathology
Analytical Cellular Pathology ONCOLOGY-CELL BIOLOGY
CiteScore
4.90
自引率
3.10%
发文量
70
审稿时长
16 weeks
期刊介绍: Analytical Cellular Pathology is a peer-reviewed, Open Access journal that provides a forum for scientists, medical practitioners and pathologists working in the area of cellular pathology. The journal publishes original research articles, review articles, and clinical studies related to cytology, carcinogenesis, cell receptors, biomarkers, diagnostic pathology, immunopathology, and hematology.
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