miR-23a impairs bone differentiation in osteosarcoma via down-regulation of GJA1.
miR-23a impairs bone differentiation in osteosarcoma via down-regulation of GJA1.
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DOI：
10.3389/fgene.2015.00233
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发表时间：
2015
影响因子：
3.7
通讯作者：
Meltzer PS
中科院分区：
文献类型：
--
作者：
Gindin Y;Jiang Y;Francis P;Walker RL;Abaan OD;Zhu YJ;Meltzer PS
骨肉瘤是儿童和青少年中最常见的骨癌类型。成骨细胞分化受损是这种侵袭性疾病的显著特征。由于生存率的改善已经基本稳定，更好地了解骨分化程序可能会提供新的治疗方法。miR-23 a ~ 27 a ~24-2，尤其是miR-23 a，与骨发育相关基因相互作用。然而，与该簇的功能获得相关的基因表达的全球变化尚未得到充分探讨。为了更好地了解miR-23 a表达与骨细胞分化之间的关系，我们在HOS细胞中进行了大规模的基因表达分析。实验结果表明，miR-23 a的过表达延迟了该系统中的分化。下游生物信息学分析鉴定了miR-23 a靶基因连接蛋白-43（Cx43/GJA 1），其是成骨细胞发育的关键细胞间信号传导的介体，受到miR-23 a水平的急性影响。连接蛋白-43在HOS细胞分化过程中上调，而在用miR-23 a转染的细胞中下调。基因表达数据的分析，在基因表达综合，揭示了Cx43是一致的成骨细胞分化过程中上调。使用荧光素酶报告基因测定在体外证实miR-23 a对Cx43 mRNA的抑制。这项工作证明了骨肉瘤中microRNA表达，细胞间信号传导和骨分化之间的新相互作用。
Osteosarcoma is the most common type of bone cancer in children and adolescents. Impaired differentiation of osteoblast cells is a distinguishing feature of this aggressive disease. As improvements in survival outcomes have largely plateaued, better understanding of the bone differentiation program may provide new treatment approaches. The miRNA cluster miR-23a~27a~24-2, particularly miR-23a, has been shown to interact with genes important for bone development. However, global changes in gene expression associated with functional gain of this cluster have not been fully explored. To better understand the relationship between miR-23a expression and bone cell differentiation, we carried out a large-scale gene expression analysis in HOS cells. Experimental results demonstrate that over-expression of miR-23a delays differentiation in this system. Downstream bioinformatic analysis identified miR-23a target gene connexin-43 (Cx43/GJA1), a mediator of intercellular signaling critical to osteoblast development, as acutely affected by miR-23a levels. Connexin-43 is up-regulated in the course of HOS cell differentiation and is down-regulated in cells transfected with miR-23a. Analysis of gene expression data, housed at Gene Expression Omnibus, reveals that Cx43 is consistently up-regulated during osteoblast differentiation. Suppression of Cx43 mRNA by miR-23a was confirmed in vitro using a luciferase reporter assay. This work demonstrates novel interactions between microRNA expression, intercellular signaling and bone differentiation in osteosarcoma.
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影响因子：
3.4
作者：
Cai, Haiqing;Lin, Lijun;Wang, Zhigang
通讯作者：
Wang, Zhigang
影响因子：
11.2
作者：
Jones KB;Salah Z;Del Mare S;Galasso M;Gaudio E;Nuovo GJ;Lovat F;LeBlanc K;Palatini J;Randall RL;Volinia S;Stein GS;Croce CM;Lian JB;Aqeilan RI
通讯作者：
Aqeilan RI
影响因子：
4.8
作者：
Hassan, Mohammad Q.;Tare, Rahul S.;Lian, Jane B.
通讯作者：
Lian, Jane B.
影响因子：
3.3
作者：
Lecanda, F;Towler, DA;Civitelli, R
通讯作者：
Civitelli, R
DOI：
10.1073/pnas.0804438105
发表时间：
2008-09-16
影响因子：
11.1
作者：
Li, Zhaoyong;Hassan, Mohammad Q.;Stein, Gary S.
通讯作者：
Stein, Gary S.