Reciprocal regulation of Hsa-miR-1 and long noncoding RNA MALAT1 promotes triple-negative breast cancer development
Reciprocal regulation of Hsa-miR-1 and long noncoding RNA MALAT1 promotes triple-negative breast cancer development
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DOI：
10.1007/s13277-015-4605-6
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发表时间：
2016-06-01
期刊：
影响因子：
--
通讯作者：
Ma, Lei
中科院分区：
文献类型：
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作者：
Jin, Chuan;Yan, Bingchuan;Ma, Lei
最近的研究表明，长链非编码RNA（lncRNA）在调节癌症的进展和转移中具有关键作用。然而，转移相关肺腺癌转录本1（MALAT 1）发挥其致癌活性的机制知之甚少，MALAT 1和microRNA之间的相互作用在很大程度上仍然未知。在本研究中，我们报道了MALAT 1在三阴性乳腺癌（TNBC）组织中上调。在体外，MALAT 1的敲低抑制增殖、运动和增加凋亡。体内研究表明，MALAT 1的敲低抑制肿瘤的生长和转移。MALAT 1高表达患者的总生存时间比MALAT 1低表达患者差。此外，我们的研究结果表明MALAT 1和miR-1之间存在相互的负对照关系：MALAT 1的下调增加了microRNA-1（miR-1）的表达，而miR-1的过表达降低了MALAT 1的表达。Slug被鉴定为miR-1的直接靶点。我们认为MALAT 1通过miR-1/slug轴发挥其功能。总之，我们提出MALAT 1可能是TNBC治疗的靶点。
Recent studies demonstrated that long noncoding RNAs (lncRNAs) have a critical role in the regulation of cancer progression and metastasis. However, little is known about the mechanism through which metastasis-associated lung adencarcinoma transcript 1 (MALAT1) exerts its oncogenic activity, and the interaction between MALAT1 and microRNA remains largely unknown. In the present study, we reported that MALAT1 was upregulated in triple-negative breast cancer (TNBC) tissues. Knockdown of MALAT1 inhibited proliferation, motility, and increased apoptosis in vitro. In vivo study indicated that knockdown of MALAT1 inhibited tumor growth and metastasis. Patients with high MALAT1 expression had poorer overall survival time than those with low MALAT1 expression. In addition, our findings demonstrate a reciprocal negative control relationship between MALAT1 and miR-1: downregulation of MALAT1 increased expression of microRNA-1 (miR-1), while overexpression of miR-1 decreased MALAT1 expression. Slug was identified as a direct target of miR-1. We proposed that MALAT1 exerted its function through the miR-1/slug axis. In summary, we proposed that MALAT1 may be a target for TNBC therapy.