lncRNA H19/miR-675 axis represses prostate cancer metastasis by targeting TGFBI
lncRNA H19/miR-675 axis represses prostate cancer metastasis by targeting TGFBI
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DOI：
10.1111/febs.12902
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发表时间：
2014-08-01
期刊：
影响因子：
5.4
通讯作者：
Yu, Jianxiu
中科院分区：
文献类型：
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作者：
Zhu, Miaojun;Chen, Qin;Yu, Jianxiu
前列腺癌是全世界男性癌症相关死亡的主要原因，并且对于晚期（转移性）前列腺癌缺乏有效的治疗选择。目前，关于长链非编码RNA在前列腺癌转移中的作用的知识有限。在这项研究中，我们发现，与非转移性前列腺上皮细胞系P69相比，转移性前列腺癌细胞系M12中的长非编码RNA H19（H19）和H19衍生的microRNA-675（miR-675）显著下调。H19在P69和PC 3细胞中的上调显著增加了miR-675的水平并抑制了细胞迁移;然而，H19在M12细胞中的异位表达不能增加miR-675的水平，因此对细胞迁移没有影响。此外，我们发现P69细胞中H19或miR-675的表达水平与转化生长因子β诱导蛋白（TGFBI）的表达呈负相关，TGFBI是一种参与癌症转移的细胞外基质蛋白。双荧光素酶报告基因检测显示miR-675直接与TGFBI mRNA的3 'UTR结合，抑制其翻译。总之，我们首次表明H19-miR-675轴作为前列腺癌转移的抑制因子，这可能对晚期前列腺癌具有诊断和治疗潜力。
Prostate cancer is a leading cause of cancer-related mortality in men worldwide and there is a lack of effective treatment options for advanced (metastatic) prostate cancer. Currently, limited knowledge is available concerning the role of long non-coding RNAs in prostate cancer metastasis. In this study, we found that long non-coding RNA H19 (H19) and H19-derived microRNA-675 (miR-675) were significantly downregulated in the metastatic prostate cancer cell line M12 compared with the non-metastatic prostate epithelial cell line P69. Upregulation of H19 in P69 and PC3 cells significantly increased the level of miR-675 and repressed cell migration; however, ectopic expression of H19 in M12 cells could not increase the level of miR-675 and therefore had no effect on cell migration. Furthermore, we found that the expression level of either H19 or miR-675 in P69 cells was negatively associated with the expression of transforming growth factor beta induced protein (TGFBI), an extracellular matrix protein involved in cancer metastasis. Dual luciferase reporter assays showed that miR-675 directly bound with 3'UTR of TGFBI mRNA to repress its translation. Taken together, we show for the first time that the H19-miR-675 axis acts as a suppressor of prostate cancer metastasis, which may have possible diagnostic and therapeutic potential for advanced prostate cancer.