Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
Int J Biol Sci. 2018 May 15;14(6):622-632. doi: 10.7150/ijbs.24223. eCollection 2018.
Breast cancer is one of the most lethal cancers in the world. The fight against breast cancer has also become a major task for medical workers. MicroRNAs (miRNAs) are often aberrantly expressed in diverse cancers and are involved in progression and metastasis. Many studies have found that miRNAs can act as oncogenes or as tumor suppressor genes. Here, we show that miR-433 is significantly decreased in breast cancer cells. In addition, we demonstrate the effects of miR-433 on breast cancer cell apoptosis, migration and proliferation in an attempt to elucidate the mechanism of action of miR-433. Moreover, Rap1a was predicted to be a potential target of miR-433 using bioinformatic approaches, and we found that the expression of Rap1a is inversely correlated with the level of miR-433. Further studies through overexpression and knockdown of Rap1a confirmed that Rap1a, as a direct target gene of miR-433, contributes to the functions of miR-433. In addition, we found that Rap1a activates the MAPK signaling pathway, which can contribute to cell migration and proliferation and can inhibit apoptosis. Overall, these findings highlight miR-433 as a tumor suppressor gene in the regulation of the progression and metastatic potential of breast cancer and may benefit the future development of therapies targeting miR-433 in breast cancer.
乳腺癌是世界上最致命的癌症之一。抗击乳腺癌也成为了医务工作者的一项主要任务。microRNAs（miRNAs）在多种癌症中常表现出异常表达，并且参与了癌症的进展和转移。许多研究发现，miRNAs 可以作为癌基因或肿瘤抑制基因发挥作用。在这里，我们表明 miR-433 在乳腺癌细胞中显著下调。此外，我们证明了 miR-433 对乳腺癌细胞凋亡、迁移和增殖的影响，试图阐明 miR-433 的作用机制。此外，通过生物信息学方法预测 Rap1a 是 miR-433 的一个潜在靶标，我们发现 Rap1a 的表达与 miR-433 的水平呈负相关。通过 Rap1a 的过表达和敲低进一步研究证实，Rap1a 作为 miR-433 的直接靶基因，有助于 miR-433 的功能。此外，我们发现 Rap1a 激活了 MAPK 信号通路，这有助于细胞迁移和增殖，并能抑制细胞凋亡。总的来说，这些发现强调了 miR-433 在调节乳腺癌的进展和转移潜能方面作为肿瘤抑制基因的作用，并且可能有助于未来针对乳腺癌中 miR-433 的治疗方法的发展。
