Inhibition of Lymphangiogenesis: A Protective Role of microRNA 146a-5p in Breast Cancer

IF 1.9 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Breast Journal Pub Date : 2024-08-21 DOI:10.1155/2024/7813083
Wenlong Liang, Haoran Wang, Baiyang Fu, Yuan Song, Zheng Zhang, Xin Liu, Yujia Lin, Jianguo Zhang
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Abstract

Breast cancer is the leading cause of death and morbidity among women. A major challenge for clinical management of breast cancer is the dissemination of breast cancer cells from the primary tumor site via lymphatic drainage, resulting in metastatic tumor spread. Recent studies have found that high expression of the microRNA miR-146a-5p is associated with better survival outcomes for breast cancer patients. However, the mechanisms for this prognostic benefit are not fully elucidated, including whether or not miR-146a-5p plays a role in suppression of lymphatic dissemination. In this study, we investigated the role and uncovered functional mechanisms of miR-146a-5p in breast cancer. We found that high expression of miR-146a-5p is associated with better clinical outcomes, specifically in the patients with N0 breast cancer. In culture, miR-146a-5p overexpression in MCF-7 breast cancer cells suppressed cell migration and lymphangiogenesis in lymphatic endothelial cells. When implanted in the mammary fat pad of mice, we observed that miR-146a-5p overexpressing MCF-7 suppressed lymphatic dissemination but had no effect on tumor progression in the primary site. This suppression was associated with fewer disseminated cancer cells and reduced lymphangiogenesis in the draining and distal lymph nodes. In conclusion, these results suggest that miR-146a-5p can exhibit a protective role against breast cancer metastasis, and it can be a therapeutic target for breast cancer.

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抑制淋巴管生成:微RNA 146a-5p在乳腺癌中的保护作用
乳腺癌是妇女死亡和发病的主要原因。乳腺癌临床治疗的一大挑战是乳腺癌细胞通过淋巴引流从原发肿瘤部位扩散,导致肿瘤转移。最近的研究发现,microRNA miR-146a-5p 的高表达与乳腺癌患者较好的生存预后有关。然而,这种预后获益的机制尚未完全阐明,包括 miR-146a-5p 是否在抑制淋巴扩散中发挥作用。在这项研究中,我们研究了 miR-146a-5p 在乳腺癌中的作用并揭示了其功能机制。我们发现,miR-146a-5p的高表达与更好的临床预后相关,尤其是在N0乳腺癌患者中。在培养过程中,miR-146a-5p 在 MCF-7 乳腺癌细胞中的过表达抑制了细胞迁移和淋巴内皮细胞的淋巴管生成。当植入小鼠乳腺脂肪垫时,我们观察到过表达 miR-146a-5p 的 MCF-7 细胞抑制了淋巴扩散,但对原发部位的肿瘤进展没有影响。这种抑制与较少的扩散癌细胞以及引流淋巴结和远端淋巴结的淋巴管生成减少有关。总之,这些结果表明,miR-146a-5p 对乳腺癌转移具有保护作用,可以作为乳腺癌的治疗靶点。
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来源期刊
Breast Journal
Breast Journal 医学-妇产科学
CiteScore
4.00
自引率
0.00%
发文量
47
审稿时长
4-8 weeks
期刊介绍: The Breast Journal is the first comprehensive, multidisciplinary source devoted exclusively to all facets of research, diagnosis, and treatment of breast disease. The Breast Journal encompasses the latest news and technologies from the many medical specialties concerned with breast disease care in order to address the disease within the context of an integrated breast health care. This editorial philosophy recognizes the special social, sexual, and psychological considerations that distinguish cancer, and breast cancer in particular, from other serious diseases. Topics specifically within the scope of The Breast Journal include: Risk Factors Prevention Early Detection Diagnosis and Therapy Psychological Issues Quality of Life Biology of Breast Cancer.
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