MicroRNA-27a functions as a tumor suppressor in renal cell carcinoma by targeting epidermal growth factor receptor

被引:30
作者
Li, Yueyan [1 ]
Li, Jie [1 ]
Sun, Xiaolei [1 ]
Chen, Jiacun [1 ]
Sun, Xiaoqing [1 ]
Zheng, Junnian [1 ]
Chen, Renfu [1 ]
机构
[1] Xuzhou Med Coll, Affiliated Hosp, Dept Urol, 99 Huaihai Rd West, Xuzhou 221002, Jiangsu, Peoples R China
关键词
microRNA; RCC; EGFR; proliferation; ONCOGENIC MICRORNA-27A; CANCER; METASTASIS; EXPRESSION; MIGRATION; INVASION; EGFR; PROLIFERATION; PATHOGENESIS; PROGRESSION;
D O I
10.3892/ol.2016.4500
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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 in vivo. 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.
引用
收藏
页码:4217 / 4223
页数:7
相关论文
共 53 条
[1]
Everolimus (RAD001) in the Treatment of Advanced Renal Cell Carcinoma: A Review [J].
Agarwala, Sanjiv S. ;
Case, Scott .
ONCOLOGIST, 2010, 15 (03) :236-245
[2]
MicroRNA signatures in human cancers [J].
Calin, George A. ;
Croce, Carlo M. .
NATURE REVIEWS CANCER, 2006, 6 (11) :857-866
[3]
miR-129-3p, as a diagnostic and prognostic biomarker for renal cell carcinoma, attenuates cell migration and invasion via downregulating multiple metastasis-related genes [J].
Chen, Xuanyu ;
Ruan, Anming ;
Wang, Xuegang ;
Han, Weiwei ;
Wang, Rong ;
Lou, Ning ;
Ruan, Hailong ;
Qiu, Bin ;
Yang, Hongmei ;
Zhang, Xiaoping .
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2014, 140 (08) :1295-1304
[4]
Oncogenic microRNA-27a is a target for anticancer agent methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate in colon cancer cells [J].
Chintharlapalli, Sudhakar ;
Papineni, Sabitha ;
Abdelrahim, Maen ;
Abudayyeh, Ala ;
Jutooru, Indira ;
Chadalapaka, Gayathri ;
Wu, Fei ;
Mertens-Talcott, Susanne ;
Vanderlaag, Kathy ;
Cho, Sung Dae ;
Smith, Roger, III ;
Safe, Stephen .
INTERNATIONAL JOURNAL OF CANCER, 2009, 125 (08) :1965-1974
[5]
The miR-17-92 Cluster is Over Expressed in and Has an Oncogenic Effect on Renal Cell Carcinoma [J].
Chow, Tsz-fung F. ;
Mankaruos, Marina ;
Scorilas, Andreas ;
Youssef, Youssef ;
Girgis, Andrew ;
Mossad, Sarah ;
Metias, Shereen ;
Rofael, Yostina ;
Honey, R. John ;
Stewart, Robert ;
Pace, Kenneth T. ;
Yousef, George M. .
JOURNAL OF UROLOGY, 2010, 183 (02) :743-751
[6]
Differential expression profiling of microRNAs and their potential involvement in renal cell carcinoma pathogenesis [J].
Chow, Tsz-Fung F. ;
Youssef, Youssef M. ;
Lianidou, Evi ;
Romaschin, Alexander D. ;
Honey, R. John ;
Stewart, Robert ;
Pace, Kenneth T. ;
Yousef, George M. .
CLINICAL BIOCHEMISTRY, 2010, 43 (1-2) :150-158
[7]
Comprehensive analysis of microRNA expression patterns in renal biopsies of lupus nephritis patients [J].
Dai, Yong ;
Sui, Weiguo ;
Lan, Huijuan ;
Yan, Qiang ;
Huang, He ;
Huang, YuanShuai .
RHEUMATOLOGY INTERNATIONAL, 2009, 29 (07) :749-754
[8]
Mechanisms of microRNA deregulation in human cancer [J].
Deng, Shan ;
Calin, George Adrian ;
Croce, Carlo M. ;
Coukos, George ;
Zhang, Lin .
CELL CYCLE, 2008, 7 (17) :2643-2646
[9]
Renal cell carcinoma development and miRNAs: a possible link to the EGFR pathway [J].
Dias, Francisca ;
Teixeira, Ana L. ;
Santos, Juliana I. ;
Gomes, Monica ;
Nogueira, Augusto ;
Assis, Joana ;
Medeiros, Rui .
PHARMACOGENOMICS, 2013, 14 (14) :1793-1803
[10]
Oncomirs - microRNAs with a role in cancer [J].
Esquela-Kerscher, A ;
Slack, FJ .
NATURE REVIEWS CANCER, 2006, 6 (04) :259-269