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Caprin-1 是一种新型的 microRNA-223 靶标,可调节人乳腺癌细胞的增殖和侵袭。

Caprin-1 is a novel microRNA-223 target for regulating the proliferation and invasion of human breast cancer cells.

机构信息

Shanghai Changning Maternity and Infant Health Hospital, No. 773 Wuyi Road, Changning District, Shanghai 200051, PR China.

出版信息

Biomed Pharmacother. 2013 Sep;67(7):629-36. doi: 10.1016/j.biopha.2013.06.006. Epub 2013 Jul 12.

Abstract

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.

摘要

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。

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