MicroRNA-218 (miR-218)是调节肿瘤进展相关过程的关键调控因子。本研究旨在探讨miR-218与表皮生长因子受体（EGFR）之间的关系，以及三阴性乳腺癌（TNBC）中的下游效应。我们评估了细胞系和公开的原发性乳腺癌基因表达数据中miR-218和EGFR的表达情况。然后，在两个TNBC细胞系中过表达miR-218，并研究其对EGFR和下游的丝裂原活化蛋白（MAP）激酶信号转导的影响。采用荧光素酶报告基因试验来表征miR-218与EGFR mRNA之间的直接结合作用。数字全息显微镜帮助研究miR-218过表达后细胞迁移和干重的变化。通过显微镜评估细胞分裂和侵袭能力，通过克隆形成实验研究miR-218过表达在辐射反应中的影响，分别研究miR-218过表达单独和与EGFR敲定联合后的情况。我们发现，在细胞系和原发性乳腺癌组织中，EGFR的表达与miR-218的水平呈反相关。miR-218过表达通过直接结合mRNA导致EGFR下调。预miR-218转染后，EGFR和下游的p44/42 MAPK信号转导的激活都会减弱。与对照相比，miR-218过表达的细胞增殖、运动性和浸润性均受到抑制，而细胞死亡和有丝分裂灾难则受到上调。相比于单独过表达miR-218的细胞，miR-218过表达和EGFR siRNA处理的细胞更加敏感于辐射。本研究表征了miR-218与EGFR之间的拮抗关系，并证明了miR-218过表达的下游功能效应，促进了抗肿瘤性的细胞变化。©2023年作者。

MicroRNA-218 (miR-218) is a key regulator of numerous processes relevant to tumor progression. In the present study, we aimed to characterize the relationship between miR-218 and the Epidermal Growth Factor Receptor (EGFR) as well as to understand downstream effects in triple-negative breast cancer (TNBC).We assessed miR-218 and EGFR expression in cell lines and publicly available primary breast cancer gene expression data. We then overexpressed miR-218 in two TNBC cell lines and investigated effects on EGFR and downstream mitogen-activated protein (MAP) kinase signaling. Luciferase reporter assay was used to characterize a direct binding interaction between miR-218 and EGFR mRNA. Digital holographic microscopy helped investigate cell migration and dry mass after miR-218 overexpression. Cell division and invasion were assessed microscopically, while radiation response after miR-218 overexpression alone or combined with additional EGFR knockdown was investigated via clonogenic assays.We found an inverse correlation between EGFR expression and miR-218 levels in cell lines and primary breast cancer tissues. MiR-218 overexpression resulted in a downregulation of EGFR via direct binding of the mRNA. Activation of EGFR and downstream p44/42 MAPK signaling were reduced after pre-miR-218 transfection. Cell proliferation, motility and invasiveness were inhibited whereas cell death and mitotic catastrophe were upregulated in miR-218 overexpressing cells compared to controls. MiR-218 overexpressing and EGFR siRNA-treated cells were sensitized to irradiation, more than miR-218 overexpressing cells alone.This study characterizes the antagonistic relationship between miR-218 and EGFR. It also demonstrates downstream functional effects of miR-218 overexpression, leading to anti-tumorigenic cellular changes.© 2023. The Author(s).