MicroRNA-203 negatively regulates c-Abl, ERK1/2 phosphorylation, and proliferation in smooth muscle cells.
MicroRNA-203 negatively regulates c-Abl, ERK1/2 phosphorylation, and proliferation in smooth muscle cells.
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DOI：
10.14814/phy2.12541
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发表时间：
2015-09
影响因子：
2.5
通讯作者：
Tang DD
中科院分区：
文献类型：
--
作者：
Liao G;Panettieri RA;Tang DD
非受体酪氨酸激酶c-Abl具有调节平滑肌细胞增殖的作用，这有助于慢性哮喘气道重塑的发展。microRNA（miRs）是一类非编码小分子RNA，通过与靶基因3′非翻译区（3′ UTR）的互补序列结合来调控基因表达。先前的分析表明miR-203能够与人c-Abl mRNA的3′ UTR结合。在本报告中，用miR-203处理减弱了人气道平滑肌（HASM）细胞中c-Abl mRNA和蛋白的表达。此外，用miR-203抑制剂转染增强了HASM细胞中c-Abl在mRNA和蛋白水平上的表达。血小板源性生长因子（PDGF）诱导HASM细胞增殖和ERK 1/2磷酸化。暴露于miR-203减弱了HASM细胞中PDGF刺激的增殖和ERK 1/2磷酸化。与对照HASM细胞相比，哮喘HASM细胞中c-Abl在蛋白和mRNA水平上的表达更高，而miR-203的水平在哮喘HASM细胞中降低。综上所述，我们目前的结果表明，miR-203是平滑肌细胞中c-Abl表达的负调节因子。miR-203通过控制c-Abl表达调节平滑肌细胞增殖，c-Abl表达反过来调节ERK 1/2的活化。
The nonreceptor tyrosine kinase c-Abl has a role in regulating smooth muscle cell proliferation, which contributes to the development of airway remodeling in chronic asthma. MicroRNAs (miRs) are small noncoding RNA molecules that regulate gene expression by binding to complementary sequences in the 3′ untranslated regions (3′ UTR) of target mRNAs. Previous analysis suggests that miR-203 is able to bind to the 3′ UTR of human c-Abl mRNA. In this report, treatment with miR-203 attenuated the expression of c-Abl mRNA and protein in human airway smooth muscle (HASM) cells. Furthermore, transfection with an miR-203 inhibitor enhanced the expression of c-Abl at mRNA and protein levels in HASM cells. Treatment with platelet-derived growth factor (PDGF) induced the proliferation and ERK1/2 phosphorylation in HASM cells. Exposure to miR-203 attenuated the PDGF-stimulated proliferation and ERK1/2 phosphorylation in HASM cells. The expression of c-Abl at protein and mRNA levels was higher in asthmatic HASM cells, whereas the level of miR-203 was reduced in asthmatic HASM cells as compared to control HASM cells. Taken together, our present results suggest that miR-203 is a negative regulator of c-Abl expression in smooth muscle cells. miR-203 regulates smooth muscle cell proliferation by controlling c-Abl expression, which in turn modulates the activation of ERK1/2.