Department of cell biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
Anat Rec (Hoboken). 2013 Dec;296(12):1842-9. doi: 10.1002/ar.22823. Epub 2013 Oct 24.
Tudor-SN is a multifunctional protein that is highly expressed in multiple cancers including breast cancer. Tudor-SN, as a component in RNA-induced splicing complex, was recently reported to regulate gene expression in a microRNA (miRNA)-dependent manner, such as let-7, miR-34a and miR-221. However, how Tudor-SN is associated with cancer development still remains largely elusive. In the present study, we explored the role of Tudor-SN in breast cancer. Stable knockdown of endogenous Tudor-SN, performed on the breast cancer cell line MDA-MB-231 by small hairpin RNA expression vectors, suppressed the in vitro migration and invasion ability of the metastatic breast cancer cell line. Interestingly, we found Tudor-SN as a miRNA regulator according to microarray analysis, and further identified that Tudor-SN negatively regulated the expression of miR-127, and consequently increased the expression of the proto-oncogene BCL6 which was a convincing target of miR-127. Moreover, overexpression of miR-127 reduced the in vitro migration and proliferation ability of breast cancer cell MDA-MB-231. Collectively, our results suggested a novel mechanism that Tudor-SN promoted metastasis and proliferation of breast cancer cells via downregulating the miR-127 expression.
Tudor-SN 是一种多功能蛋白，在包括乳腺癌在内的多种癌症中高表达。Tudor-SN 作为 RNA 诱导剪接复合物的一个组成部分，最近被报道以 miRNA 依赖的方式调节基因表达，如 let-7、miR-34a 和 miR-221。然而，Tudor-SN 如何与癌症发展相关仍然很大程度上难以捉摸。在本研究中，我们探讨了 Tudor-SN 在乳腺癌中的作用。通过短发夹 RNA 表达载体在乳腺癌细胞系 MDA-MB-231 中稳定敲低内源性 Tudor-SN，抑制了转移性乳腺癌细胞系的体外迁移和侵袭能力。有趣的是，我们根据微阵列分析发现 Tudor-SN 是一种 miRNA 调节因子，进一步鉴定出 Tudor-SN 负调控 miR-127 的表达，从而增加了 miR-127 的原癌基因 BCL6 的表达，这是 miR-127 的一个可信靶标。此外，miR-127 的过表达降低了乳腺癌细胞 MDA-MB-231 的体外迁移和增殖能力。综上所述，我们的研究结果表明，Tudor-SN 通过下调 miR-127 的表达促进了乳腺癌细胞的转移和增殖，这为乳腺癌的治疗提供了新的靶点。
