Long Noncoding RNA HOTAIR Modulates MiR-206-mediated Bcl-w Signaling to Facilitate Cell Proliferation in Breast Cancer.
Long Noncoding RNA HOTAIR Modulates MiR-206-mediated Bcl-w Signaling to Facilitate Cell Proliferation in Breast Cancer.
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DOI：
10.1038/s41598-017-17492-x
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发表时间：
2017-12-08
影响因子：
4.6
通讯作者：
Wang D
中科院分区：
文献类型：
--
作者：
Ding W;Ren J;Ren H;Wang D
HOX转录本反义RNA（HOTAIR）参与了多种癌症的发生。促生存蛋白Bcl-w经常在癌症发展中发现。然而，HOTAIR对乳腺癌中Bcl-w的影响没有很好的记录。在本研究中，我们首先评估了临床乳腺癌组织中HOTAIR水平与Bcl-w表达之间的相关性。我们观察到Bcl-w在乳腺癌组织中的表达水平明显高于其配对的非癌组织。此外，在临床乳腺癌样本中HOTAIR水平与Bcl-w水平呈正相关。正如预期的那样，我们观察到HOTAIR能够上调乳腺癌细胞中Bcl-w的表达。在机制上，我们发现miR-206能够通过直接与Bcl-w mRNA的3′UTR结合来抑制Bcl-w的表达。有趣的是，HOTAIR可以通过在转录后水平隔离miR-206来增加Bcl-w的表达。在功能上，我们的数据显示HOTAIR通过miR-206诱导的Bcl-w促进了乳腺癌细胞的增殖。因此，我们得出结论，HOTAIR上调Bcl-w，以提高乳腺癌细胞增殖，通过螯合miR-206。我们的发现为HOTAIR介导的乳腺癌机制提供了新的见解。
LncRNA HOX transcript antisense RNA (HOTAIR) is involved in lots of cancers. The pro-survival protein Bcl-w is frequently found in cancer development. However, the effect of HOTAIR on Bcl-w in breast cancer is not well documented. In this study, we first evaluated the correlation between HOTAIR level and Bcl-w expression in clinical breast cancer tissues. We observed that the expression levels of Bcl-w were much higher in the breast cancer samples than that in their paired noncancerous tissues. Moreover, the levels of HOTAIR were positively associated with those of Bcl-w in clinical breast cancer samples. As expected, we observed that HOTAIR was able to up-regulate the expression of Bcl-w in breast cancer cells. Mechanistically, we found that miR-206 was capable of inhibiting the expression of Bcl-w by directly binding to the 3′UTR of Bcl-w mRNA. Interestingly, HOTAIR could increase the expression of Bcl-w through sequestering miR-206 at post-transcriptional level. Functionally, our data showed that HOTAIR-induced Bcl-w by miR-206 facilitated the proliferation of breast cancer cells. Thus, we conclude that HOTAIR up-regulates Bcl-w to enhance cell proliferation through sequestering miR-206 in breast cancer. Our finding provides new insights into the mechanism of breast cancer mediated by HOTAIR.
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