Liang Wenlong, Wang Haoran, Fu Baiyang, Song Yuan, Zhang Zheng, Liu Xin, Lin Yujia, Zhang Jianguo
Department of Breast Surgery Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Hepatobiliary Surgery Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Breast J. 2024 Aug 21;2024:7813083. doi: 10.1155/2024/7813083. eCollection 2024.
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.
乳腺癌是女性死亡和发病的主要原因。乳腺癌临床治疗的一个主要挑战是乳腺癌细胞通过淋巴引流从原发肿瘤部位扩散，导致转移性肿瘤扩散。最近的研究发现，微小RNA miR-146a-5p的高表达与乳腺癌患者更好的生存结果相关。然而，这种预后益处的机制尚未完全阐明，包括miR-146a-5p是否在抑制淋巴扩散中起作用。在本研究中，我们调查了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结果相关，特别是在N0期乳腺癌患者中。在培养中，MCF-7乳腺癌细胞中miR-146a-5p的过表达抑制了细胞迁移和淋巴管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。这种抑制与较少的播散癌细胞和引流及远端淋巴结中淋巴管生成减少有关。总之，这些结果表明miR-146a-5p可以对乳腺癌转移发挥保护作用，并且它可以成为乳腺癌的治疗靶点。
