Shanghai Changning Maternity and Infant Health Hospital, No. 773 Wuyi Road, Changning District, Shanghai 200051, PR China.
Biomed Pharmacother. 2013 Sep;67(7):629-36. doi: 10.1016/j.biopha.2013.06.006. Epub 2013 Jul 12.
MicroRNAs (miRNAs) are 21-22 nucleotides regulatory small non-coding RNAs that inhibit gene expression by binding to complementary sequences especially the 3' untranslated region (3'UTR) of mRNA. One miRNA can target many messenger RNAs, leading to a complex metabolic network. Previous studies have shown that miRNA-223 regulates migration and invasion of tumor cells and targets cytoplasmic activation/proliferation-associated protein-1 (Caprin-1). In the present study, we detected the expression of miRNA-223 and Caprin-1 in MCF-7, T-47D and MDA-MB-231 cancer cell lines, and MCF-10A normal breast cell line, and analyzed the role of miRNA-223 in Caprin-1-induced proliferation and invasion of human breast cancer cells. We found that miRNA-223 expression levels are significantly lower in MCF-7, T-47D and MDA-MB-231 cancer cells than in MCF-10A normal breast cells, while Caprin-1 expression is higher in cancer cells than in normal breast cells. The most malignant cancer cell line MDA-MB-231 has the lowest expression of miR-223, but the highest expression of Caprin-1. Further, we found that miR-223 targets the 3'UTR of Caprin-1 miRNA and down-regulates the expression of Caprin-1. We also found that over-expression of Caprin-1 can promote the proliferation and the invasion of breast cancer cells, but miRNA-223 can inhibit the proliferation and the invasion. miRNA-223-induced inhibition can be reversed by ectopic over-expression of Caprin-1. These findings suggest that miR-223 may suppress the proliferation and invasion of cancer cells by directly targeting Caprin-1. Our study also indicates that expression levels of miR-223 and Caprin-1 can be used to predict the state of cancer in breast cancer patient.
微小 RNA(miRNAs)是 21-22 个核苷酸的调节性小非编码 RNA,通过与 mRNA 的互补序列,特别是 3'非翻译区(3'UTR)结合来抑制基因表达。一个 miRNA 可以靶向许多信使 RNA,从而导致复杂的代谢网络。先前的研究表明,miRNA-223 调节肿瘤细胞的迁移和侵袭,并靶向细胞质激活/增殖相关蛋白-1(Caprin-1)。在本研究中,我们检测了 miRNA-223 和 Caprin-1 在 MCF-7、T-47D 和 MDA-MB-231 癌细胞系以及 MCF-10A 正常乳腺细胞系中的表达,并分析了 miRNA-223 在 Caprin-1 诱导的人乳腺癌细胞增殖和侵袭中的作用。我们发现,miRNA-223 在 MCF-7、T-47D 和 MDA-MB-231 癌细胞系中的表达水平明显低于 MCF-10A 正常乳腺细胞,而 Caprin-1 在癌细胞系中的表达高于正常乳腺细胞。最恶性的癌细胞系 MDA-MB-231 具有最低的 miR-223 表达,但具有最高的 Caprin-1 表达。进一步,我们发现 miR-223 靶向 Caprin-1 的 3'UTR,并下调 Caprin-1 的表达。我们还发现,Caprin-1 的过表达可以促进乳腺癌细胞的增殖和侵袭,而 miRNA-223 可以抑制增殖和侵袭。Caprin-1 的过表达可以逆转 miRNA-223 诱导的抑制作用。这些发现表明,miR-223 可能通过直接靶向 Caprin-1 来抑制癌细胞的增殖和侵袭。我们的研究还表明,miR-223 和 Caprin-1 的表达水平可用于预测乳腺癌患者的癌症状态。