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学科主题: 基础医学
题名:
MicroRNA 145 may play an important role in uveal melanoma cell growth by potentially targeting insulin receptor substrate-1
作者: 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
发表日期: 2014-04-20
DOI: 10.3760/cma.j.issn.0366-6999.20133206
卷: 127, 期:8, 页:1410-1416
收录类别: SCI
文章类型: Article
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
英文摘要:

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.

语种: 英语
所属项目编号: 81272981 ; 7112031
项目资助者: National Natural Science Foundation of China ; Natural Sciences Fundation of Beijing, China
WOS记录号: WOS:000335936700004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50753
Appears in Collections:基础医学院_细胞生物学系_期刊论文

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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

Recommended Citation:
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.
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