Department of Oncology, Traditional Chinese Medical Hospital of Siyang County, Siyang 223700, Jiangsu, China.
Safety Assessment and Research Center for Drug, Pesticide and Veterinary Drug of Jiangsu Province, Nanjing Medical University, Nanjing 211166, Jiangsu, China.
Cell Signal. 2018 Apr;44:33-42. doi: 10.1016/j.cellsig.2018.01.013. Epub 2018 Jan 12.
Dishevelled-associated activator of morphogenesis 1 (Daam1) is a formin protein and participates in regulating cell migration of triple-negative breast cancer (TNBC) cells. The specific miRNA targeting Daam1 and mediating cell migration and invasion remains obscure. This experiment investigated the suppressive role of miR-613 in TNBC cells. The luciferase activity of Daam1 3'-untranslated region (3'-UTR) based reporters constructed in HEK-293T and MCF-7 cells suggested that Daam1 was the target gene of miR-613. Overexpressed miR-613 reduced the protein level of Daam1, weakened RhoA activity, and retarded the cell migration, cell invasion and colony formation of TNBC cells. Overexpression of Daam1 or RhoA rescued cell migration and invasion in miR-613-overexpressed TNBC cells, but failed to reverse colony formation. MiR-613 was significantly downregulated in breast cancer tissues compared with that in adjacent normal tissues. This downregulation in TNBC tissues and lymphnode metastatic breast cancer tissues was more obvious than that in non-TNBC tissues and non-metastatic cancer tissues, respectively. MiR-613 weakens the resistance of TNBC cells against paclitaxel rather than adriamycin, cyclophosphamide, docetaxel, and kaempferol. Taken together, miR-613 is involved in cell migration and invasion of TNBC cells via targeting Daam1/RhoA signaling pathway.
形态发生激活因子 1（Daam1）是一种formin 蛋白，参与调节三阴性乳腺癌（TNBC）细胞的迁移。但针对 Daam1 并介导细胞迁移和侵袭的特定 miRNA 仍不清楚。本实验研究了 miR-613 在 TNBC 细胞中的抑制作用。在 HEK-293T 和 MCF-7 细胞中构建的 Daam1 3'-非翻译区（3'-UTR）报告基因的荧光素酶活性表明，Daam1 是 miR-613 的靶基因。过表达 miR-613 降低了 Daam1 的蛋白水平，减弱了 RhoA 的活性，并减缓了 TNBC 细胞的迁移、侵袭和集落形成。在 miR-613 过表达的 TNBC 细胞中过表达 Daam1 或 RhoA 可挽救细胞迁移和侵袭，但不能逆转集落形成。与相邻正常组织相比，miR-613 在乳腺癌组织中显著下调。在 TNBC 组织和淋巴结转移性乳腺癌组织中的下调程度明显高于非 TNBC 组织和非转移性癌症组织。miR-613 减弱了 TNBC 细胞对紫杉醇的耐药性，而不是对阿霉素、环磷酰胺、多西他赛和山奈酚的耐药性。总之，miR-613 通过靶向 Daam1/RhoA 信号通路参与 TNBC 细胞的迁移和侵袭。
