hsa-miR-29c* is linked to the prognosis of malignant pleural mesothelioma.
hsa-miR-29c* is linked to the prognosis of malignant pleural mesothelioma.
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DOI：
10.1158/0008-5472.can-09-3993
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发表时间：
2010-03-01
期刊：
影响因子：
11.2
通讯作者：
Aharonov R
中科院分区：
文献类型：
--
作者：
Pass HI;Goparaju C;Ivanov S;Donington J;Carbone M;Hoshen M;Cohen D;Chajut A;Rosenwald S;Dan H;Benjamin S;Aharonov R
由于无法预测恶性间皮瘤的预后，临床医生无法为可能从这种方法中受益的最合适的个体提供积极的多模式治疗。我们调查了特定的microRNAs(MiRs)是否可以将一组主要接受手术治疗的间皮瘤分为预后良好或预后不良两类。使用定制的microRNA平台分析了44个训练集和98个间皮瘤的测试集，以及9个间皮瘤细胞系和3个正常间皮细胞系。研究了潜在预后microRNAs的功能含义和下游靶点。在训练组和测试组中，hsa-miR-29c*是手术细胞减少术后进展时间和存活率的独立预后因素。MiR在上皮性间皮瘤中的表达水平较高，这种miR的表达水平可以将这种组织学类型的患者分为预后不同的组。Hsa-miR-29c*的高表达预示着更好的预后，而间皮瘤细胞系中miR的过表达导致细胞的增殖、迁移、侵袭和集落形成显著减少。此外，间皮瘤的主要表观遗传调控是由hsa-miR-29c*介导的，并通过下调DNA甲基转移酶和上调去甲基化基因来证实。单个microRNA有可能成为间皮瘤的预后生物标志物，对这些发现的验证以及对其下游靶点的研究可能为未来的潜在治疗提供洞察力。
The inability to forecast outcomes for malignant mesothelioma prevents clinicians from providing aggressive multimodality therapy to the most appropriate individuals who may benefit from such an approach. We investigated whether specific microRNAs (miRs) could segregate a largely surgically-treated group of mesotheliomas into good or bad prognosis categories. A training set of 44 and a test set of 98 mesothelioma tumors were analyzed by a custom microRNA platform, along with 9 mesothelioma cell lines and 3 normal mesothelial lines. Functional implications as well as downstream targets of potential prognostic microRNAs were investigated. In both the training and test sets, hsa-miR-29c* was an independent prognostic factor for time to progression as well as survival after surgical cytoreduction. The miR was expressed at higher levels in epithelial mesothelioma, and the level of this miR could segregate patients with this histology into groups with differing prognosis. Increased expression of hsa-miR-29c* predicted a more favorable prognosis, and overexpression of the miR in mesothelioma cell lines resulted in significantly decreased proliferation, migration, invasion, and colony formation. Moreover, major epigenetic regulation of mesothelioma is mediated by hsa-miR-29c* and was demonstrated through downregulation of DNA methyltransferases as well as upregulation of demethylating genes. A single microRNA has the potential to be a prognostic biomarker in mesothelioma, and validation of these findings as well as investigation of its downstream targets may give insight for potential therapies in the future.