miR-520b Regulates Migration of Breast Cancer Cells by Targeting Hepatitis B X-interacting Protein and Interleukin-8
miR-520b Regulates Migration of Breast Cancer Cells by Targeting Hepatitis B X-interacting Protein and Interleukin-8
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miR-520b 通过靶向乙型肝炎 X 相互作用蛋白和白细胞介素 8 调节乳腺癌细胞的迁移
DOI：
10.1074/jbc.m110.204131
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发表时间：
2011-04-15
影响因子：
4.8
通讯作者：
Ye, Lihong
中科院分区：
文献类型：
--
作者：
Hu, Nan;Zhang, Jianli;Ye, Lihong
microRNA在肿瘤转移中起重要作用。最近，我们报道了miR-520 b的水平与乳腺癌细胞的转移潜能呈负相关。在这项研究中，我们研究了miR-520 b在乳腺癌细胞迁移中的作用。我们发现，miR-520 b抑制了具有高转移潜力的乳腺癌细胞的迁移，包括MDA-MB-231和LM-MCF-7细胞，尽管miR-520 b的抑制增强了低转移潜力MCF-7细胞的迁移。我们进一步发现，miR-520 B直接靶向B X相互作用蛋白（HBXIP）或白细胞介素-8（IL-8）的3 '非翻译区（3' UTR），据报道，这有助于细胞迁移。令人惊讶的是，组织阵列分析显示，75%（38：49）和94%（36：38）的乳腺癌组织和转移性淋巴组织分别对HBXIP表达呈阳性。此外，HBXIP的过表达能够促进MCF-7细胞的迁移。有趣的是，HBXIP能够通过NF-κ B调节IL-8的转录，这表明miR-520 B的两个靶基因在功能上是相连的。此外，我们发现miR-520 B可以通过靶向HBXIP间接调节IL-8的转录。因此，我们得出结论，miR-520 b通过HBXIP和IL-8靶向网络参与调节乳腺癌细胞迁移，其中HBXIP通过刺激NF-κ B介导的IL-8表达促进迁移。这些研究指出HBXIP是乳腺癌的潜在治疗靶点。
MicroRNAs play important roles in tumor metastasis. Recently, we reported that the level of miR-520b is inversely related to the metastatic potential of breast cancer cells. In this study, we investigated the role of miR-520b in breast cancer cell migration. We found that miR-520b suppressed the migration of breast cancer cells with high metastatic potential, including M DA-MB-231 and LM-MCF-7 cells, although the inhibition of miR-520b enhanced the migration of low metastatic potential MCF-7 cells. We further discovered that miR-520b directly targets the 3'-untranslated region (3'UTR) of either hepatitis B X-interacting protein (HBXIP) or interleukin-8 (IL-8), which has been reported to contribute to cell migration. Surprisingly, tissue array assays showed that 75% (38:49) and 94% (36:38) of breast cancer tissues and metastatic lymph tissues, respectively, were positive for HBXIP expression. Moreover, overexpression of HBXIP was able to promote the migration of MCF-7 cells. Interestingly, HBXIP was able to regulate IL-8 transcription by NF-kappa B, suggesting that the two target genes of miR-520b are functionally connected, In addition, we found that miR-520b could indirectly regulate IL-8 transcription by targeting HBXIP. Thus, we conclude that miR-520b is involved in regulating breast cancer cell migration by targeting HBXIP and IL-8 via a network in which HBXIP promotes migration by stimulating NF-kappa B-mediated IL-8 expression. These studies point to HBXIP as a potential therapeutic target for breast cancer.