Department of Medical Biology, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromso, Norway.
Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromso, Norway.
Sci Rep. 2024 Oct 23;14(1):25022. doi: 10.1038/s41598-024-75557-0.
MicroRNAs are involved in breast cancer development and progression, holding potential as biomarkers and therapeutic targets or tools. The roles of miR-20a-5p, a member of the oncogenic miR-17-92 cluster, remain poorly understood in the context of breast cancer. In this study, we elucidate the role of miR-20a-5p in breast cancer by examining its associations with breast cancer risk factors and clinicopathological features, and its functional roles in vitro. Tissue microarrays from 313 CAMO cohort breast cancer surgical specimens were constructed, in situ hybridization was performed and miR-20a-5p expression was semiquantitatively scored in tumor stromal fibroblasts, and in the cytoplasm and nuclei of cancer cells. In vitro analysis of the effect of miR-20a-5p transfection on proliferation, migration and invasion was performed in three breast cancer cell lines. High stromal miR-20a-5p was associated with higher Ki67 expression, and higher odds of relapse, compared to low expression. Compared to postmenopausal women, women who were premenopausal at diagnosis had higher odds of high stromal and cytoplasmic miR-20a-5p expression. Cytoplasmic miR-20a-5p was significantly associated with tumor grade. In tumors with high cytoplasmic miR-20a-5p expression compared to low expression, there was a tendency towards having a basal-like subtype and high Ki67. In contrast, high nuclear miR-20a-5p in cancer cells was associated with smaller tumor size and lower odds of lymph node metastasis, compared to low nuclear expression. Transfection with miR-20a-5p in breast cancer cell lines led to increased migration and invasion in vitro. While the majority of our results point towards an oncogenic role, some of our findings indicate that the associations of miR-20a-5p with breast cancer related risk factors and outcomes may vary based on tissue- and subcellular location. Larger studies are needed to validate our findings and further investigate the clinical utility of miR-20a-5p.
微小 RNA 参与乳腺癌的发生和发展，具有作为生物标志物和治疗靶点或工具的潜力。miR-17-92 致癌簇的成员 miR-20a-5p 在乳腺癌中的作用仍知之甚少。在这项研究中，我们通过检查其与乳腺癌危险因素和临床病理特征的关联及其在体外的功能作用，阐明了 miR-20a-5p 在乳腺癌中的作用。构建了来自 313 名 CAMO 队列乳腺癌手术标本的组织微阵列，进行原位杂交，在肿瘤间质成纤维细胞、癌细胞的细胞质和核中对 miR-20a-5p 表达进行半定量评分。在三种乳腺癌细胞系中进行了 miR-20a-5p 转染对增殖、迁移和侵袭影响的体外分析。与低表达相比，高基质 miR-20a-5p 与更高的 Ki67 表达和更高的复发几率相关。与绝经后女性相比，诊断时处于绝经前的女性有更高的高基质和细胞质 miR-20a-5p 表达的几率。细胞质 miR-20a-5p 与肿瘤分级显著相关。与低表达相比，高细胞质 miR-20a-5p 表达的肿瘤有倾向于具有基底样亚型和高 Ki67。相比之下，与低核表达相比，癌细胞中高核 miR-20a-5p 与肿瘤体积较小和淋巴结转移几率较低相关。在乳腺癌细胞系中转染 miR-20a-5p 导致体外迁移和侵袭增加。虽然我们的大多数结果表明它具有致癌作用，但我们的一些发现表明，miR-20a-5p 与乳腺癌相关危险因素和结果的关联可能因组织和亚细胞位置而异。需要更大的研究来验证我们的发现并进一步研究 miR-20a-5p 的临床应用。
