Differential microRNA expression profiling of mesothelioma and expression analysis of miR-1 and miR-214 in mesothelioma
Differential microRNA expression profiling of mesothelioma and expression analysis of miR-1 and miR-214 in mesothelioma
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DOI：
10.3892/ijo.2016.3358
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发表时间：
2016-04-01
影响因子：
5.2
通讯作者：
Takeshima, Yukio
中科院分区：
文献类型：
--
作者：
Amatya, Vishwa Jeet;Mawas, Amany Sayed;Takeshima, Yukio
恶性间皮瘤是一种高度侵袭性的癌症，预后差，对目前可用的治疗方法无效。大多数晚期侵袭性肿瘤患者不能接受手术切除和/或现有的抗癌治疗，因此需要开发新的有效的治疗方案。MicroRNAs(MiRNAs)的异常表达被认为与间皮瘤的发生和侵袭性有关。我们利用TaqMan miRNA表达阵列分析了间皮瘤细胞系中miRNA的表达，发现有大量的miRNAs表达上调或缺失。我们通过单独的miRNA检测和SmartFlare miRNA探针验证了miR-182和miR-183在间皮瘤细胞系中的表达增加。我们进一步研究了间皮瘤细胞中未表达的miR-1和miR-214基因。将miRNA模拟物(hsa-miR-1模拟物和hsa-miR-214模拟物)导入间皮瘤细胞ACC-Meso-1和CRL5915，可抑制细胞的生长、侵袭和迁移。我们注意到了miR-1和miR-214两种miRNAs的靶基因PIM1，并且发现它在间皮瘤细胞中过表达，Western印迹分析显示，miR-1和miR-214模拟转染间皮瘤细胞系显示PIM1下调。MiR-1和miR-214可能在间皮瘤的发生发展中起一定作用，可作为间皮瘤的候选治疗靶点。
Malignant mesothelioma is a highly aggressive cancer with poor prognosis and refractory to currently available therapies. Most of the patients with advanced invasive nature are not amenable to surgical resection and/or available anticancer therapy, thus development of novel effective therapeutic regimes is needed. Aberrant expression of microRNAs (miRNAs) has been proposed to contribute to carcinogenesis and aggressiveness of mesothelioma. We analyzed miRNA expression in mesothelioma cell lines using TaqMan miRNA expression array and found significant number of miRNAs, which showed increased or lost expression. We validated the increased expression of miR-182, and miR-183 in mesothelioma cell lines by individual miRNA assays and SmartFlare miRNA probes. We further investigated the miR-1, and miR-214, which were not expressed in mesothelioma cells by real-time RT-PCR. Transfection of mesothelioma cells, ACC-Meso-1 and CRL5915, with miRNA mimic (hsa-miR-1 mimic and hsa-miR-214 mimic) led to inhibition of cell growth, invasion and migration. We paid attention to PIM1, the target gene of both miR-1 and miR-214 miRNAs and which was found overexpressed in mesothelioma cells, and miR-1 and miR-214 mimic transfection of mesothelioma cell lines showed downregulation of PIM1 by western blot analysis. The miRNAs, miR-1 and miR-214, may play a role in carcinogenesis of mesothelioma thus might be considered as candidate therapeutic targets in mesothelioma.