MicroRNA-125a inhibits cell growth by targeting glypican-4
文献类型:期刊论文
作者 | Feng, Chao1,2; Li, Jie2; Ruan, Jinlan1; Ding, Kan2![]() |
刊名 | GLYCOCONJUGATE JOURNAL
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出版日期 | 2012-10 |
卷号 | 29期号:7页码:503-511 |
关键词 | miR-125a glypican-4 ERK1/2 AKT |
ISSN号 | 0282-0080 |
DOI | 10.1007/s10719-012-9387-0 |
文献子类 | Article |
英文摘要 | Heparan sulfate proteoglycan (HSPG), such as glypican, plays a role as a co-receptor for growth factor to influence cells proliferation. However the mechanism is still vague. Micro-RNAs (miRNAs) regulate cell proliferation. Their capacity to direct the translation and stability of targeted transcripts can dramatically influence cellular physiological function. To explore how the function of glypican is regulated involved in cell proliferation, glypican-4 was chosen with a bioinformatics search identifying targeting seed sequences for miR-125a within the 3'-untranslated regions (3'UTR). Indeed, luciferase constructs containing the 3'UTR of glypican-4 demonstrated around 54 % less activity in miR-125a expressing cells relative to the controls. The expression of glypican-4 at both the transcript and protein level was down-regulated by transition trasfection of miR-125a in the human embryonic kidney cell line 293T (HEK293T). Although cell proliferation of HEK293T was not influenced by the silence of glypican-4, DNA synthesis in response to FGF2 in the cells was attenuated by knockdown of glypican-4 using siRNA technique. Further study showed that phosphorylation of ERK1/2 and AKT was suppressed by overexpressing miR-125a, whereas the suppressed MAPK and AKT signaling could be recovered by anti-miR-125a treatment. Both DNA synthesis and cell proliferation were impaired by the inhibitor of ERK1/2 signaling. MTT assay demonstrated that the cell proliferation was impaired by miR-125a overexpression, however, rescued by anti-miR-125a in HEK293T cells. These results disclosed new function of miR-125a by targeting gene glypican-4 in cell growth process and illustrated the feasibility of using miRNAs as a therapeutic strategy to suppress cells proliferation. |
WOS关键词 | HEPARAN-SULFATE PROTEOGLYCANS ; CANCER-CELLS ; PHOSPHORYLATION ; FIBROBLASTS ; SYNDECAN-1 ; GENES |
资助项目 | National Natural Science Foundation of China (NSFC)[81171914] ; National Science Fund for Distinguished Young Scholars in China[81125025] |
WOS研究方向 | Biochemistry & Molecular Biology |
语种 | 英语 |
WOS记录号 | WOS:000308356000005 |
出版者 | SPRINGER |
源URL | [http://119.78.100.183/handle/2S10ELR8/277930] ![]() |
专题 | 药理学第三研究室 |
通讯作者 | Ding, Kan |
作者单位 | 1.Huazhong Univ Sci & Technol, Tongji Med Ctr, Coll Pharm, Hubei Key Lab Nat Med Chem & Resource Evaluat, Wuhan 430030, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Glycochem & Glycobiol Lab, Shanghai 201203, Peoples R China; |
推荐引用方式 GB/T 7714 | Feng, Chao,Li, Jie,Ruan, Jinlan,et al. MicroRNA-125a inhibits cell growth by targeting glypican-4[J]. GLYCOCONJUGATE JOURNAL,2012,29(7):503-511. |
APA | Feng, Chao,Li, Jie,Ruan, Jinlan,&Ding, Kan.(2012).MicroRNA-125a inhibits cell growth by targeting glypican-4.GLYCOCONJUGATE JOURNAL,29(7),503-511. |
MLA | Feng, Chao,et al."MicroRNA-125a inhibits cell growth by targeting glypican-4".GLYCOCONJUGATE JOURNAL 29.7(2012):503-511. |
入库方式: OAI收割
来源:上海药物研究所
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