Oma cells. Molecular Cancer 2013 12:155.Submit your next manuscript to BioMed Central and take full advantage of:?Convenient online submission ?Thorough peer review ?No space constraints or color figure charges ?Immediate publication on acceptance ?Inclusion in PubMed, CAS, Scopus and Google Scholar ?Research which is freely Ro4402257 chemical information available for redistributionSubmit your manuscript at www.biomedcentral.com/submit
Xu et al. PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25112874 Molecular Cancer 2014, 13:109 http://www.molecular-cancer.com/content/13/1/RESEARCHOpen AccessDownregulation of microRNA-182-5p contributes to renal cell carcinoma proliferation via activating the AKT/FOXO3a signaling pathwayXin Xu, Jian Wu, Shiqi Li, Zhenghui Hu, Xianglai Xu, Yi Zhu, Zhen Liang, Xiao Wang, Yiwei Lin, Yeqing Mao, Hong Chen, Jindan Luo, Ben Liu, Xiangyi Zheng* and Liping Xie*AbstractBackground: Emerging evidence has suggested that dysregulation of miR-182-5p may contribute to tumor development and progression in several types of human cancers. However, its role in renal cell carcinoma (RCC) is still unknown. Methods: Quantitative RT-PCR was used to quantify miR-182-5p expression in RCC clinical tissues. Bisulfite sequencing PCR was used for DNA methylation analysis. The CCK-8, colony formation, flow cytometry, and a xenograft model were performed. Immunohistochemistry was conducted using the peroxidase and DAB methods. A miR-182-5p target was determined by luciferase reporter assays, quantitative RT-PCR, and Western blotting. Results: miR-182-5p is frequently down-regulated in human RCC tissues. Epigenetic modulation may be involved in the regulation of miR-182-5p expression. Enforced expression of miR-182-5p in RCC cells significantly inhibited the proliferation and tumorigenicity in vitro and in vivo. Additionally, overexpression of miR-182-5p induced G1-phase arrest via inhibition of AKT/FOXO3a signaling. Moreover, FLOT1 was confirmed as a target of miR-182-5p. Silencing FLOT1 by small interfering RNAs phenocopied the effects of miR-182-5p overexpression, whereas restoration of FLOT1 in miR-182-5p -overexpressed RCC cells partly reversed the suppressive effects of miR-182-5p. Conclusions: These findings highlight an important role for miR-182-5p in the pathogenesis of RCC, and restoration of miR-182-5p could be considered as a potential therapeutic strategy for RCC therapy. Keywords: Renal cell carcinoma, Proliferation, Microrna-182-5p, FLOTBackground Renal cell carcinoma (RCC) is the most common type of adult kidney cancer, and clear cell RCC represents the most common renal cancer histology. The incidence and mortality rates of kidney cancer have increased in recent years, with an expected 271,000 newly-diagnosed cases and 116,000 deaths in 2008 worldwide [1]. About one-third of RCC patients are diagnosed with metastatic disease and up to 50 of patients develop metastatic disease [2] with a very poor prognosis because of the refractory nature of RCC to the current treatment regimens [3]. Therefore, it is crucial to identify novel therapeutic targets, including non-coding* Correspondence: [email protected]; [email protected] Department of Urology, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou 310003, Zhejiang Province, ChinaRNAs (ncRNA) in RCC, to develop more effective treatment options for this fatal disease. MicroRNAs (miRNAs) are a class of small, endogenous, noncoding RNAs that are approximately 22 nucleotides in length and make up a novel class of ge.
