Amatya Vishwa Jeet, Mawas Amany Sayed, Kushitani Kei, Mohi El-Din Mouchira M, Takeshima Yukio
Department of Pathology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
Department of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, South Valley University, Qena, Egypt.
Int J Oncol. 2016 Apr;48(4):1599-607. doi: 10.3892/ijo.2016.3358. Epub 2016 Jan 26.
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.
恶性间皮瘤是一种侵袭性很强的癌症，预后较差，对目前可用的治疗方法具有耐药性。大多数具有晚期侵袭性的患者不适合手术切除和/或现有的抗癌治疗，因此需要开发新的有效治疗方案。有人提出，微小RNA（miRNA）的异常表达有助于间皮瘤的致癌作用和侵袭性。我们使用TaqMan miRNA表达阵列分析了间皮瘤细胞系中的miRNA表达，发现大量miRNA的表达增加或缺失。我们通过单个miRNA检测和SmartFlare miRNA探针验证了间皮瘤细胞系中miR-182和miR-183表达的增加。我们进一步研究了通过实时逆转录聚合酶链反应在间皮瘤细胞中未表达的miR-1和miR-214。用miRNA模拟物（hsa-miR-1模拟物和hsa-miR-214模拟物）转染间皮瘤细胞ACC-Meso-1和CRL5915可导致细胞生长、侵袭和迁移受到抑制。我们关注了miR-1和miR-214这两种miRNA的靶基因PIM1，发现其在间皮瘤细胞中过表达，通过蛋白质印迹分析，miR-1和miR-214模拟物转染间皮瘤细胞系显示PIM1表达下调。miR-1和miR-214这两种miRNA可能在间皮瘤的致癌过程中发挥作用，因此可能被视为间皮瘤的候选治疗靶点。
