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间充质干细胞向成骨细胞分化过程中的微小RNA表达及其调控网络。

MicroRNAs expression and their regulatory networks during mesenchymal stem cells differentiation toward osteoblasts.

作者信息

Vimalraj S, Selvamurugan N

机构信息

Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur, Tamil Nadu, India.

Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur, Tamil Nadu, India.

出版信息

Int J Biol Macromol. 2014 May;66:194-202. doi: 10.1016/j.ijbiomac.2014.02.030. Epub 2014 Feb 20.

Abstract

MicroRNAs (miRNAs) are small endogenous noncoding RNAs which regulate mRNAs post-transcriptionally. In this study, a selective number of miRNAs was investigated for their expression and intracellular regulatory networks involved in differentiation of human mesenchymal stem cells (hMSCs) toward osteoblasts. The expression of miR-424, miR-106a, miR-148a, let-7i and miR-99a miRNAs was found to be specific in hMSCs; whereas expression of miR-15b, miR-24, miR-130b, miR-30c, and miR-130a miRNAs was found to be specific in differentiated osteoblasts. A bioinformatics approach identified that the MAPK pathway was mostly targeted by hMSCs specific miRNAs; whereas JAK-STAT, p53, Focal adhesion, gap junction, ubiquitin mediated proteolysis pathways were targeted by osteblastic specific miRNAs. Altering expression of osteoblast specific miRNA (miR-15b) promoted adipogenesis and myogenesis lineages. Thus, we suggest that miRNAs' regulatory networks and their target genes might provide an insight of their role during differentiation of hMSCs toward osteoblasts, and alteration in the expression of miRNAs would be a valuable approach for controlling osteoblast differentiation.

摘要

微小RNA(miRNA)是一类内源性非编码小RNA,可在转录后水平调控mRNA。在本研究中,我们研究了部分miRNA在人骨髓间充质干细胞(hMSC)向成骨细胞分化过程中的表达及其细胞内调控网络。发现miR-424、miR-106a、miR-148a、let-7i和miR-99a在hMSC中表达具有特异性;而miR-15b、miR-24、miR-130b、miR-30c和miR-130a在分化的成骨细胞中表达具有特异性。生物信息学方法鉴定出丝裂原活化蛋白激酶(MAPK)信号通路是hMSC特异性miRNA的主要作用靶点;而成骨细胞特异性miRNA的作用靶点包括Janus激酶-信号转导及转录激活因子(JAK-STAT)、p53、粘着斑、缝隙连接、泛素介导的蛋白水解途径。改变成骨细胞特异性miRNA(miR-15b)的表达可促进脂肪生成和肌生成谱系。因此,我们认为miRNA的调控网络及其靶基因可能有助于深入了解其在hMSC向成骨细胞分化过程中的作用,而改变miRNA的表达可能是控制成骨细胞分化的一种有价值的方法。

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