miR-519 suppresses tumor growth by reducing HuR levels.
miR-519 suppresses tumor growth by reducing HuR levels.
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DOI：
10.4161/cc.9.7.11164
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发表时间：
2010-04-01
期刊：
影响因子：
--
通讯作者：
Gorospe M
中科院分区：
文献类型：
--
作者：
Abdelmohsen K;Kim MM;Srikantan S;Mercken EM;Brennan SE;Wilson GM;Cabo Rd;Gorospe M
rna结合蛋白HuR在许多癌症中含量很高。最近发现，microRNA miR-519可抑制HuR的表达，从而在不影响HuR mRNA丰度的情况下有效降低HuR的翻译。在这里，我们检测了HuR和miR-519在卵巢癌、肺癌和肾脏的癌症和邻近健康组织中的水平。在三个样本收集中，与健康组织相比，癌症标本的HuR水平显著升高，HuR mRNA浓度不变，miR-519水平显著降低。通过使用人宫颈癌细胞进行测试，miR-519减少了胸腺小鼠的肿瘤发生。与对照细胞形成的肿瘤相比，过表达miR-519的细胞形成的肿瘤明显变小，而表达miR-519水平降低的细胞形成的肿瘤明显变大。通过降低HuR获得了miR-519诱导的HuR降低对其肿瘤抑制作用至关重要的证据，因为即使降低miR-519丰度，miR-519沉默的细胞也能形成明显更小的肿瘤，并且不能形成大的肿瘤。总之，我们的数据显示miR-519在很大程度上是通过抑制HuR表达来抑制肿瘤发生的。
The RNA-binding protein HuR is highly abundant in many cancers. HuR expression was recently found to be repressed by microRNA miR-519, which potently lowered HuR translation without influencing HuR mRNA abundance. Here, we examined the levels of HuR and miR-519 in pairs of cancer and adjacent healthy tissues from ovary, lung, and kidney. In the three sample collections, the cancer specimens showed dramatically higher HuR levels, unchanged HuR mRNA concentrations, and markedly reduced miR-519 levels, when compared with healthy tissues. As tested using human cervical carcinoma cells, miR-519 reduced tumorigenesis in athymic mice. Compared with the tumors arising from control cells, cells overexpressing miR-519 formed significantly smaller tumors, while cells expressing reduced miR-519 levels gave rise to substantially larger tumors. Evidence that the miR-519-elicited reduction of HuR was critical for its tumor suppressor influence was obtained by reducing HuR, as HuR-silenced cells formed markedly smaller tumors and were unable to form large tumors even after lowering miR-519 abundance. Together, our data reveal that miR-519 inhibits tumorigenesis in large part by repressing HuR expression.
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