Department of Molecular Medicine and Medical Biotechnology, "Federico II" University of Naples, 80131 Naples, Italy.
Percuros BV, 2333 CL Leiden, The Netherlands.
Int J Mol Sci. 2020 Mar 27;21(7):2313. doi: 10.3390/ijms21072313.
Breast cancer is the most frequent malignancy in females in terms of both incidence and mortality. Underlying the high mortality rate is the presence of cancer stem cells, which divide indefinitely and are resistant to conventional chemotherapies, so causing tumor relapse. In the present study, we identify miR-216a-5p as a downregulated microRNA in breast cancer stem cells vs. the differentiated counterpart. We demonstrate that overexpression of miR-216a-5p impairs stemness markers, mammosphere formation, ALDH activity, and the level of (), which plays a significant role in breast cancer progression and metastasis by leading to the release of pro-inflammatory molecules, such as interleukin 6 (IL-6). Indeed, miR-216a regulates the crosstalk between cancer cells and the cells of the microenvironment, in particular cancer-associated fibroblasts (CAFs), through regulation of the TLR4/IL6 pathway. Thus, miR-216a has an important role in the regulation of stem phenotype, decreasing stem-like properties and affecting the cross-talk between cancer cells and the tumor microenvironment.
乳腺癌是女性中发病率和死亡率最高的恶性肿瘤。导致高死亡率的原因是癌症干细胞的存在，癌症干细胞无限分裂且对常规化疗具有抗性，从而导致肿瘤复发。在本研究中，我们发现 miR-216a-5p 在乳腺癌干细胞中相较于分化细胞呈下调表达。我们证明过表达 miR-216a-5p 可削弱干细胞标志物、乳腺球形成、ALDH 活性和 () 水平，后者通过导致促炎分子（如白细胞介素 6 (IL-6)）的释放，在乳腺癌的进展和转移中起着重要作用。事实上，miR-216a 通过调节 TLR4/IL6 通路来调控癌细胞与微环境细胞（特别是癌相关成纤维细胞，CAFs）之间的串扰。因此，miR-216a 在调节干细胞表型方面发挥着重要作用，降低了干细胞样特性并影响了癌细胞与肿瘤微环境之间的相互作用。
