MiR-409-3p/Rab10/BRCA1轴抑制子宫内膜癌的恶性转化

IF 2.5 4区综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES

Journal of Radiation Research and Applied Sciences Pub Date : 2025-08-15 DOI:10.1016/j.jrras.2025.101877

Yibing Fan , Jiayu Wen , Li Shi, Yingqing Dai

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引用次数: 0

摘要

目前的研究表明，miR-409-3p通过调节关键癌基因发挥抑癌作用，但其在子宫内膜癌（EC）中的机制尚不清楚。目的本研究通过靶向ras相关蛋白rab1 (Rab10)，探讨miR-409-3p对乳腺癌易感基因1 （BRCA1）表达的影响，评估miR-409-3p在抑制EC恶性转化中的作用。材料和方法以RL95-2和HEC-1B EC细胞系和正常子宫内膜基质细胞（ESCs）为实验对象。使用慢病毒载体操纵miR-409-3p的表达。CCK-8检测细胞增殖，Transwell检测侵袭，real-time PCR和Western blot检测基因表达。流式细胞术评价细胞周期变化。丙二醛（MDA）和超氧化物歧化酶（SOD）检测用于评估氧化应激水平。结果上调smir -409-3p可使Rab10的表达降低2.5倍(P <；0.001)， BRCA1水平升高1.8倍(P <；0.01)，抑制EC细胞的增殖和侵袭(P <；0.05)。此外，BRCA1上调被Rab10过表达逆转(P <；0.05)。BRCA1上调可诱导细胞周期阻滞，减轻氧化应激，提示具有保护作用(P <；0.05)。BRCA1的敲低逆转了miR-409-3p/Rab10信号的抗癌作用(P <；0.05)，证实了其在该通路中的关键作用。本研究首次证明miR-409-3p通过rab10介导的BRCA1上调抑制EC恶性肿瘤，揭示了EC的新治疗轴。这些发现强调了miR-409-3p作为一种潜在的治疗靶点，对未来妇科癌症治疗的研究和临床应用具有重要意义。

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MiR-409-3p/Rab10/BRCA1 axis inhibits malignant transformation of endometrial carcinoma

Background

Current research suggests that miR-409-3p plays the role of a tumor suppressor by regulating key oncogenes, but its mechanism in endometrial carcinoma (EC) remains unclear.

Objectives

This study evaluated how miR-409-3p functions in inhibiting the malignant transformation of EC by targeting ras-related protein Rab-1 (Rab10) and exploring its impact on breast cancer susceptibility gene 1 (BRCA1) expression.

Materials and methods

Experiments were performed in RL95-2 and HEC-1B EC cell lines and normal endometrial stromal cells (ESCs). miR-409-3p expression was manipulated using lentiviral vectors. CCK-8 assays assessed cell proliferation, Transwell assays measured invasion, real-time PCR and Western blot analyzed gene expression. Flow cytometry evaluated cell cycle changes. Malondialdehyde (MDA) and superoxide dismutase (SOD) assays were used to assess oxidative stress levels.

Results

MiR-409-3p upregulation reduced Rab10 expression by 2.5-fold (P < 0.001) and increased BRCA1 levels by 1.8-fold (P < 0.01), inhibiting EC cell expansion and invasion (P < 0.05). Further, BRCA1 upregulation was reversed by Rab10 overexpression (P < 0.05). BRCA1 upregulation induced cell cycle arrest and alleviated oxidative stress, suggesting a protective role (P < 0.05). Knockdown of BRCA1 reversed the anticancer impact of miR-409-3p/Rab10 signaling (P < 0.05), confirming its critical role in the pathway.

Conclusion

This study is the first to demonstrate that miR-409-3p suppresses EC malignancy via Rab10-mediated BRCA1 upregulation, revealing a novel therapeutic axis for EC. These findings highlight miR-409-3p as a potential therapeutic target and implications for future research and clinical applications in gynecological cancer treatment.

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来源期刊

Journal of Radiation Research and Applied Sciences MULTIDISCIPLINARY SCIENCES-

自引率

5.90%

发文量

130

审稿时长

16 weeks

期刊介绍： Journal of Radiation Research and Applied Sciences provides a high quality medium for the publication of substantial, original and scientific and technological papers on the development and applications of nuclear, radiation and isotopes in biology, medicine, drugs, biochemistry, microbiology, agriculture, entomology, food technology, chemistry, physics, solid states, engineering, environmental and applied sciences.