Macedo Taciane, Silva-Oliveira Renato J, Silva Viviane A O, Vidal Daniel O, Evangelista Adriane F, Marques Marcia M C
Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP 14784-400, Brazil.
Barretos School of Health Sciences, Barretos, SP 14785-002, Brazil.
Oncol Lett. 2017 Jul;14(1):1054-1060. doi: 10.3892/ol.2017.6265. Epub 2017 May 26.
Breast cancer (BC) is a leading cause of cancer-associated mortality in females worldwide. MicroRNAs (miRNAs or miRs), a type of non-coding RNA, have been reported to be important in the regulation of onset and progression. Several studies have implicated the role of miR-183 and miR-494 in different types of cancer. However, the biological functions of these miRNAs in BC remain largely unknown. In the present study, the expression of both miRNAs was assessed in the MDA-MB-231 and MDA-MB-468 BC cell lines. It was hypothesized that miR-183 and miR-494 serve an important role in regulating the expression of key genes associated with the metastatic phenotype of BC cells. To further understand their role, the expression of these miRNAs was restored in selected BC cell lines. Functional assays revealed that overexpression of miR-183 or miR-494 modulated the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells . Additionally, retinoblastoma 1 (RB1) was identified to be a downstream target of both miRNAs by analysis. Western blotting revealed that upregulation of miR-183 was associated with downregulation of RB1 protein in MDA-MB-231 cells. In conclusion, the present results support the hypothesis that miR-183 and miR-494 serve a pivotal role in BC metastasis, and that miR-183 may act as an oncogene by targeting RB1 protein in MDA-MB-231 cells.
乳腺癌（BC）是全球女性癌症相关死亡的主要原因。微小RNA（miRNA或miR）是一种非编码RNA，据报道在疾病的发生和发展调控中起重要作用。多项研究表明miR-183和miR-494在不同类型癌症中发挥作用。然而，这些miRNA在乳腺癌中的生物学功能仍 largely未知。在本研究中，评估了这两种miRNA在MDA-MB-231和MDA-MB-468乳腺癌细胞系中的表达。据推测，miR-183和miR-494在调节与乳腺癌细胞转移表型相关的关键基因表达中起重要作用。为了进一步了解它们的作用，在选定的乳腺癌细胞系中恢复了这些miRNA的表达。功能分析表明，miR-183或miR-494的过表达调节了MDA-MB-231和MDA-MB-468细胞的增殖和迁移。此外，通过分析确定视网膜母细胞瘤1（RB1）是这两种miRNA的下游靶点。蛋白质印迹法显示，miR-183的上调与MDA-MB-231细胞中RB1蛋白的下调有关。总之，目前的结果支持以下假设：miR-183和miR-494在乳腺癌转移中起关键作用，并且miR-183可能通过靶向MDA-MB-231细胞中的RB1蛋白而作为癌基因发挥作用。
