MicroRNA-125a inhibits cell growth by targeting glypican-4
MicroRNA-125a inhibits cell growth by targeting glypican-4
复制标题
MicroRNA-125a 通过靶向磷脂酰肌醇蛋白聚糖 4 抑制细胞生长
DOI：
10.1007/s10719-012-9387-0
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发表时间：
2012-10-01
影响因子：
3
通讯作者：
Ding, Kan
中科院分区：
文献类型：
--
作者：
Feng, Chao;Li, Jie;Ding, Kan
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 formiR-125awithin the 3′-untranslated regions (3′UTR). Indeed, luciferase constructs containing the 3′UTR of glypican-4 demonstrated around 54 % less activity inmiR-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 ofmiR-125ain 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 ERK1/2and AKT was suppressed by overexpressingmiR-125a, whereas the suppressed MAPK and AKT signaling could be recovered by anti-miR-125atreatment. Both DNA synthesis and cell proliferation were impaired by the inhibitor of ERK1/2signaling. MTT assay demonstrated that the cell proliferation was impaired bymiR-125aoverexpression, however, rescued by anti-miR-125ain 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.
