期刊
MOLECULAR CANCER
卷 13, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/1476-4598-13-109
关键词
Renal cell carcinoma; Proliferation; Microrna-182-5p; FLOT1
资金
- National Key Clinical Specialty Construction Project of China
- Key medical disciplines of Zhejiang province
- Combination of traditional Chinese and Western medicine key disciplines of Zhejiang Province [2012-XK-A23]
- Health sector scientific research special project [201002010]
- National Natural Science Foundation of China [81372773, 81101717]
- Scientific Research Fund of Zhejiang Provincial Education Department [Y201120149]
- Zhejiang Provincial Natural Science Foundation of China [Y2110120, LY12H05006]
Background: 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.
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