Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA
Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA
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DOI：
10.1128/mcb.00242-06
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发表时间：
2006-11-01
影响因子：
5.3
通讯作者：
Saunders, Grady F.
中科院分区：
文献类型：
--
作者：
Hossain, Anwar;Kuo, Macus T.;Saunders, Grady F.
微小RNA（MicroRNAs）是一个庞大的家族，其成员是长度约为22个核苷酸的非编码RNA，在包括人类在内的多种真核生物中表达，并且在发育和疾病过程中具有重要作用。我们发现微小RNA Mir - 17 - 5p与AIB1（因“在乳腺癌1中扩增”而得名）的信使RNA（mRNA）具有广泛的互补性。细胞培养实验表明，Mir - 17 - 5p主要通过抑制翻译来下调AIB1的表达。Mir - 17 - 5p在乳腺癌细胞系中的表达水平较低。我们还发现，Mir - 17 - 5p对AIB1的下调导致雌激素受体介导的以及不依赖雌激素受体的基因表达降低，以及乳腺癌细胞增殖减少。Mir - 17 - 5p还完全消除了胰岛素样生长因子1介导的乳腺癌细胞的非贴壁依赖性生长。我们的研究结果表明，Mir - 17 - 5p在乳腺癌细胞中具有肿瘤抑制因子的作用。
MicroRNAs are an extensive family of similar to 22-nucleotide-long noncoding RNAs expressed in a wide range of eukaryotes, including humans, and they are important in development and disease. We found that microRNA Mir-17-5p has extensive complementarity to the mRNA of AIB1 (named for "amplified in breast cancer 1"). Cell culture experiments showed that AIB1 expression was downregulated by Mir-17-5p, primarily through translational inhibition. Expression of Mir-17-5p was low in breast cancer cell lines. We also found that downregulation of AIB1 by Mir-17-5p resulted in decreased estrogen receptor-mediated, as well as estrogen receptor-independent, gene expression and decreased proliferation of breast cancer cells. Mir-17-5p also completely abrogated the insulin-like growth factor 1-mediated, anchorage-independent growth of breast cancer cells. Our results reveal that Mir-17-5p has a role as a tumor suppressor in breast cancer cells.