miRNA-145/miRNA-205 inhibits proliferation and invasion of uveal melanoma cells by targeting NPR1/CDC42
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Wen-Bin Wei. Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing Tongren Hospital, Capital Medical University, Dongjiaomin Xiang No.1, Dongcheng District, Beijing 100730, China. weiwnbintr@163.com

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Supported by National Natural Science Foundation of China (No.81570891); Beijing Natural Science Foundation (No.7204245; No.7151003); Scientific Research Common Program of Beijing Municipal Commission of Education (No.KM202010025018); Beijing Municipal Administration of Hospitals’ Youth Programme (No.QMS20190202); Beijing Municipal Administration of Hospitals, Ascent Plan (No.DFL20150201); Advanced Health Care Professionals Development Project of Beijing Municipal Health Bureau (2014-2-003); The Capital Health Research and Development of Special (2016-1-2051); Beijing Dongcheng District Outstanding Talents Cultivating Plan (2018).

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    Abstract:

    AIM: To investigate the role of microRNA-145 (miRNA-145) and microRNA-205 (miRNA-205) in proliferation and invasion of uveal melanoma (UM) cells. METHODS: The expression level of miRNA-145 and miRNA-205 from samples of UM patients were determined by real-time polymerase chain reaction (RT-PCR). The growth and invasion inhibitory effects were observed by the transfection of UM cells with miRNA-145 and miRNA-205. Several epithelial-to-mesenchymal transition (EMT) -related proteins were screened by Western blotting. UM clinical samples from The Cancer Genome Atlas (TCGA) were applied to search for potential protein interaction. Pearson’s correlation analysis was applied to estimate co-expression between genes. Dual-luciferase reporter assay was used to verify the binding sites on target protein for miRNA-145 and miRNA-205. RESULTS: The expression levels of miRNA-145 and miRNA-205 in the samples from patients with UM were significantly lower than those in the normal tissue samples. Significant growth and invasion inhibitory effects were observed in human UM cells with miRNA-145 and miRNA-205 overexpression. The miRNA-145 and miRNA-205 could decrease the expression level of cell division control protein 42 (CDC42). After database searching and sequence alignment, we identified that Neuropilin 1 (NRP1) had binding sites for both miRNA-145 and miRNA-205. CONCLUSION: The miRNA-145 and miRNA-205 can reduce the proliferation, migration and invasion of UM cells by targeting the mRNA of its upstream protein NRP1 to down-regulate the expression level of CDC42.

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Yang Li, Jing-Ting Luo, Yue-Ming Liu, et al. miRNA-145/miRNA-205 inhibits proliferation and invasion of uveal melanoma cells by targeting NPR1/CDC42. Int J Ophthalmol, 2020,13(5):718-724

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Publication History
  • Received:January 26,2020
  • Revised:March 15,2020
  • Adopted:
  • Online: March 30,2020
  • Published: