Li Yueyan, Li Jie, Sun Xiaolei, Chen Jiacun, Sun Xiaoqing, Zheng Junnian, Chen Renfu
Department of Urology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
Oncol Lett. 2016 Jun;11(6):4217-4223. doi: 10.3892/ol.2016.4500. Epub 2016 Apr 26.
Numerous studies have suggested that microRNAs (miRNAs) are vital in the development of various types of human cancers, including renal cell carcinoma (RCC), and the regulation of tumor progression and invasion. However, the effect of miRNA-27a (miR-27a) on the tumorigenesis of RCC is unclear. The aim of the present study was to investigate the function of miR-27a and identify its possible target genes in RCC cells. In the present study, cell proliferation, migration and invasion and the percentage of apoptotic cells were detected by methylthiazol tetrazolium assays, Annexin V analysis, wound-healing assays and Transwell invasion assays. Western blot analysis was performed to validate the protein expression level and assess whether the epidermal growth factor receptor (EGFR) was a target gene of miR-27a. A tumor xenograft animal model was used to detect the role of miR-27a on RCC cell growth . The present study demonstrated that miR-27a significantly suppressed human RCC 786-O cell proliferation and induced cell apoptosis. Restoration of miR-27 also resulted in 786-O cell migration and invasion inhibition. Furthermore, upregulated miR-27a attenuated RCC tumor growth in the tumor xenograft animal model. The present results suggested that miR-27a functions as a tumor suppressor in RCC. The western blot analysis assay revealed that EGFR was a novel target of miR-27a. The growth suppression of RCC cells was attributed partly to the downregulation of the cell cycle by ERFR inhibition. The present findings may aid in the understanding of the molecular mechanism of miR-27a in the tumorigenesis of RCC, and may provide novel diagnostic and therapeutic options for RCC.
大量研究表明，微小RNA（miRNA）在包括肾细胞癌（RCC）在内的各种人类癌症的发生发展以及肿瘤进展和侵袭的调控中起着至关重要的作用。然而，miRNA-27a（miR-27a）对RCC肿瘤发生的影响尚不清楚。本研究的目的是探讨miR-27a在RCC细胞中的功能，并确定其可能的靶基因。在本研究中，通过甲基噻唑四氮唑法、膜联蛋白V分析、伤口愈合试验和Transwell侵袭试验检测细胞增殖、迁移、侵袭以及凋亡细胞的百分比。进行蛋白质印迹分析以验证蛋白质表达水平，并评估表皮生长因子受体（EGFR）是否为miR-27a的靶基因。使用肿瘤异种移植动物模型检测miR-27a对RCC细胞生长的作用。本研究表明，miR-27a显著抑制人RCC 786-O细胞增殖并诱导细胞凋亡。miR-27的恢复还导致786-O细胞迁移和侵袭受到抑制。此外，上调的miR-27a在肿瘤异种移植动物模型中减弱了RCC肿瘤的生长。目前的结果表明，miR-27a在RCC中起肿瘤抑制作用。蛋白质印迹分析试验显示，EGFR是miR-27a的一个新靶标。RCC细胞的生长抑制部分归因于通过ERFR抑制导致的细胞周期下调。本研究结果可能有助于理解miR-27a在RCC肿瘤发生中的分子机制，并可能为RCC提供新的诊断和治疗选择。
