Journal of cancer research and clinical oncology · 2014
miR-145 functions as tumor suppressor and targets two oncogenes, ANGPT2 and NEDD9, in renal cell carcinoma.
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Lu Ruijing, Ji Ziliang, Li Xiaoqing, Zhai Qingna, Zhao Chunjuan, Jiang Zhimao, Zhang Shiqiang, Nie Liping, Yu Zhendong
Аннотация
PURPOSE: Abnormal expression of miRNAs is closely related to a variety of human cancers. The purpose of this study is to identify new tumor suppressor miRNA and elucidate its physiological function and mechanism in renal cell carcinoma (RCC).
METHODS: The expression of miR-145 in 45 RCC and adjacent normal tissues was performed by quantitative RT-PCR. Cell proliferation, migration, invasion, apoptosis and cycle assays were carried out for functional analysis after miR-145 transfection. Two target genes of miR-145 were identified by luciferase reporter assay. The altered expression of 84 epithelial to mesenchymal transition (EMT)-related genes after miR-145 transfection was detected by RT(2) Profiler EMT PCR array.
RESULTS: The expression of miR-145 was downregulated in RCC compared to their normal adjacent tissues. Restoring miR-145 expression in RCC cell lines dramatically suppressed cell proliferation, migration and invasion, and induced cell apoptosis and G2-phase arrest. We further validated those miR-145 targets two oncogenes, ANGPT2 and NEDD9 in RCC. In addition, miR-145 was found to regulate numerous genes involved in the EMT.
CONCLUSIONS: These findings demonstrate that miR-145 functions as tumor suppressor in RCC, suggesting that miR-145 may be a potential therapeutic target for RCC.
METHODS: The expression of miR-145 in 45 RCC and adjacent normal tissues was performed by quantitative RT-PCR. Cell proliferation, migration, invasion, apoptosis and cycle assays were carried out for functional analysis after miR-145 transfection. Two target genes of miR-145 were identified by luciferase reporter assay. The altered expression of 84 epithelial to mesenchymal transition (EMT)-related genes after miR-145 transfection was detected by RT(2) Profiler EMT PCR array.
RESULTS: The expression of miR-145 was downregulated in RCC compared to their normal adjacent tissues. Restoring miR-145 expression in RCC cell lines dramatically suppressed cell proliferation, migration and invasion, and induced cell apoptosis and G2-phase arrest. We further validated those miR-145 targets two oncogenes, ANGPT2 and NEDD9 in RCC. In addition, miR-145 was found to regulate numerous genes involved in the EMT.
CONCLUSIONS: These findings demonstrate that miR-145 functions as tumor suppressor in RCC, suggesting that miR-145 may be a potential therapeutic target for RCC.
Предметные рубрики MeSH
Adaptor Proteins, Signal TransducingAdultAgedAngiopoietin-2Anticarcinogenic AgentsApoptosisBase SequenceCarcinoma, Renal CellCell CycleCell MovementCell ProliferationDown-RegulationEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticGenes, Tumor SuppressorHumansKidney NeoplasmsMaleMicroRNAsMiddle AgedMolecular Sequence DataNeoplasm InvasivenessNeoplasm StagingOncogenesPhosphoproteinsReverse Transcriptase Polymerase Chain Reaction