微小RNA-96通过抑制成骨细胞中的肝素结合表皮生长因子-表皮生长因子受体信号通路来促进成骨分化。

miR-96 promotes osteogenic differentiation by suppressing HBEGF-EGFR signaling in osteoblastic cells.

作者信息

Yang Mingfu, Pan Yong, Zhou Yue

机构信息

Department of Orthopaedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.

出版信息

FEBS Lett. 2014 Dec 20;588(24):4761-8. doi: 10.1016/j.febslet.2014.11.008. Epub 2014 Nov 15.

DOI:10.1016/j.febslet.2014.11.008

PMID:25451232

Abstract

MicroRNAs (miRNAs) are a class of small non-coding RNAs with important roles in various biological and pathological processes, including osteoblast differentiation. Here, we identified miR-96 as a positive regulator of osteogenic differentiation in a mouse osteoblastic cell line (MC3T3-E1) and in mouse bone marrow-derived mesenchymal stem cells. Moreover, we found that miR-96 down-regulates post-transcriptional expression of heparin-binding EGF-like growth factor (HB-EGF) by specifically binding to the 3'untranslated region of HB-EGF mRNA. Furthermore, in MC3T3-E1 cells, miR-96-induced HB-EGF down-regulation suppressed the phosphorylation of epidermal growth factor receptor (EGFR) and of extracellular signal-regulated kinase 1 (ERK1) and AKT, which both lie downstream of EGFR activation. Taken together, miR-96 promotes osteogenic differentiation by inhibiting HB-EGF and by blocking the HB-EGF-EGFR signaling pathway in osteoblastic cells.

摘要

微小RNA（miRNA）是一类小的非编码RNA，在包括成骨细胞分化在内的各种生物学和病理过程中发挥重要作用。在此，我们确定miR-96是小鼠成骨细胞系（MC3T3-E1）和小鼠骨髓间充质干细胞中成骨分化的正向调节因子。此外，我们发现miR-96通过特异性结合肝素结合表皮生长因子样生长因子（HB-EGF）mRNA的3'非翻译区来下调其转录后表达。此外，在MC3T3-E1细胞中，miR-96诱导的HB-EGF下调抑制了表皮生长因子受体（EGFR）以及细胞外信号调节激酶1（ERK1）和AKT的磷酸化，这两者都位于EGFR激活的下游。综上所述，miR-96通过抑制HB-EGF和阻断成骨细胞中的HB-EGF-EGFR信号通路来促进成骨分化。