Downregulation of microRNA-182-5p contributes to renal cell carcinoma proliferation via activating the AKT/FOXO3a signaling pathway

• Published in: Molecular cancer Vol. 13; no. 1; p. 109
• Main Authors: Xu, Xin, Wu, Jian, Li, Shiqi, Hu, Zhenghui, Xu, Xianglai, Zhu, Yi, Liang, Zhen, Wang, Xiao, Lin, Yiwei, Mao, Yeqing, Chen, Hong, Luo, Jindan, Liu, Ben, Zheng, Xiangyi, Xie, Liping
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 17.05.2014; BioMed Central
• Subjects: Analysis; Animals; Base Sequence; Carcinoma, Renal cell; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - mortality; Carcinoma, Renal Cell - pathology; Care and treatment; Cell cycle; Cell Proliferation; Cloning; Deoxyribonucleic acid; Development and progression; Diagnosis; DNA; DNA methylation; Epigenesis, Genetic; Epigenetic inheritance; Epigenetics; Experiments; Female; Forkhead Box Protein O3; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; G1 Phase Cell Cycle Checkpoints; Gene Expression Regulation, Neoplastic; Genes; Genetic research; Humans; Immunohistochemistry; Islands; Kidney cancer; Kidney Neoplasms - genetics; Kidney Neoplasms - metabolism; Kidney Neoplasms - mortality; Kidney Neoplasms - pathology; Male; Melanoma; Membrane Proteins - antagonists & inhibitors; Membrane Proteins - genetics; Membrane Proteins - metabolism; Metastasis; Methylation; Mice; Mice, Nude; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Molecular Sequence Data; Mortality; Neoplasm Transplantation; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Rodents; Signal Transduction; Studies; Sulfites; Survival Analysis; Japan
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/1476-4598-13-109

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. 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. 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. 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.