|MicroRNA 145 may play an important role in uveal melanoma cell growth by potentially targeting insulin receptor substrate-1|
|Li Yang1,2; Huang Qiming1,2; Shi Xuehui1,2; Jin Xiang1,2; Shen Li3,4; Xu Xiaolin1,2; Wei Wenbin1,2|
|关键词||Uveal Melanoma Microrna Array Mir-145 Insulin Receptor Substrate-1|
|刊名||CHINESE MEDICAL JOURNAL|
|WOS标题词||Science & Technology|
|类目[WOS]||Medicine, General & Internal|
|研究领域[WOS]||General & Internal Medicine|
|关键词[WOS]||EXPRESSION SIGNATURE ; BREAST-CANCER ; MIGRATION ; SUPPRESSES ; MIR-145 ; TUMORS ; OVEREXPRESSION ; PROLIFERATION ; METASTASIS ; INVASION|
Background MicroRNAs (miRNAs) contribute to tumorigenesis by acting as either oncogenes or tumor suppressor genes. In this Study, we investigated the role of miR-145 in the pathogenesis of uveal melanoma.
Methods Expression profiles of miRNAs in uveal melanoma were performed using Agilent miRNA array. Quantitative real-time polymerase chain reaction was used to screen The expression levels of miR-145 in normal uveal tissue, uveal melanoma tissue, and uveal melanoma cell lines. Lenti-virus expression system was used to construct MUM-2B and OCM-1 cell lines with stable overexpression of miR-145. Cell proliferation, cell cycle, and cell apoptosis of these miR-145 overexpression cell lines were examined by MTT assay and flow cytometry respectively. The target genes of miR-145 were predicted by bioinformatics and confirmed using a luciferase reporter assay. The expression of insulin-like growth factor-1 receptor (IGF-1R), insulin receptor substrate-1 (IRS-1) proteins was determined by Western blotting analysis. IRS-1 was knocked down in OCM-1 cells. TUNEL, BrdU, and flow cytometry assay were performed in IRS-1 knocked down OCM-1 cell lines to analyze its function.
Results Forty-seven miRNAs were up regulated in uveal melanoma and 61 were down regulated. miR-145 expression was significantly lower in uveal melanoma sample and the cell lines were compared with normal uveal sample. Overexpression of miR-145 suppressed cell proliferation by blocking the G1 phase entering S phase in uveal melanoma cells, and promoted uveal melanoma cell apoptosis. IRS-1 was identified as a potential target of miR-145 by dual luciferase reporter assay. Knocking down of IRS-1 had similar effect as overexpression of miR-145.
Conclusion miR-145 might act as a tumor suppressor in uveal melanoma, and downregulation of the target IRS-1 might be a potential mechanism.
|项目编号||81272981 ; 7112031|
|资助机构||National Natural Science Foundation of China ; Natural Sciences Fundation of Beijing, China|
|作者单位||1.Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing 100730, Peoples R China|
2.Beijing Key Lab Ophthalmol & Visual Sci, Beijing 100730, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Dept Cell Biol, Beijing 100191, Peoples R China
4.Peking Univ, Stem Cell Res Ctr, Beijing 100191, Peoples R China
|Li Yang,Huang Qiming,Shi Xuehui,et al. MicroRNA 145 may play an important role in uveal melanoma cell growth by potentially targeting insulin receptor substrate-1[J]. CHINESE MEDICAL JOURNAL,2014,127(8):1410-1416.|
|APA||Li Yang.,Huang Qiming.,Shi Xuehui.,Jin Xiang.,Shen Li.,...&Wei Wenbin.(2014).MicroRNA 145 may play an important role in uveal melanoma cell growth by potentially targeting insulin receptor substrate-1.CHINESE MEDICAL JOURNAL,127(8),1410-1416.|
|MLA||Li Yang,et al."MicroRNA 145 may play an important role in uveal melanoma cell growth by potentially targeting insulin receptor substrate-1".CHINESE MEDICAL JOURNAL 127.8(2014):1410-1416.|