MIR144 and MIR451 regulate human erythropoiesis via RAB14.
MIR144 and MIR451 regulate human erythropoiesis via RAB14.
复制标题
DOI：
10.1111/bjh.13164
复制
发表时间：
2015-02
影响因子：
6.5
通讯作者：
Civin CI
中科院分区：
文献类型：
--
作者：
Kim M;Tan YS;Cheng WC;Kingsbury TJ;Heimfeld S;Civin CI
MIR 144和MIR 451的表达水平在红细胞生成期间增加，这是从斑马鱼到人类的保守模式。由于这两种miR由相同的多顺反子转录物表达，我们在人红系细胞中单独和一起操纵MIR 144和MIR 451以研究它们对人红细胞生成的影响。内源性人MIR 451的抑制导致红系（CD 71 hiCD 235 ahiCD 34 −）细胞数量减少，与先前在斑马鱼和小鼠中的研究一致。此外，MIR 144的抑制损害了人类红细胞分化，这与在斑马鱼和小鼠研究中MIR 144对红细胞生成的功能性影响最小不同。在这项研究中，我们发现RAB 14是MIR 144和MIR 451的直接靶点。随着MIR 144和MIR 451表达在人红细胞生成期间增加，RAB 14蛋白表达降低。增强的RAB 14表达表型模拟MIR 144和/或MIR 451消耗的作用，而shRNA介导的RAB 14敲低保护细胞免受MIR 144和/或MIR 451消耗介导的红细胞生成抑制。在人红细胞生成过程中，RAB 14敲低增加了红系细胞的频率和数量，增加了β-血红蛋白表达，并降低了CBFA 2 T3表达。总之，我们利用MIR 144和MIR 451来鉴定RAB 14作为人红细胞生成的新型生理抑制剂。
Expression levels of MIR144 and MIR451 increase during erythropoiesis, a pattern that is conserved from zebrafish to humans. As these two miRs are expressed from the same polycistronic transcript, we manipulated MIR144 and MIR451 in human erythroid cells individually and together to investigate their effects on human erythropoiesis. Inhibition of endogenous human MIR451 resulted in decreased numbers of erythroid (CD71hiCD235ahiCD34−) cells, consistent with prior studies in zebrafish and mice. In addition, inhibition of MIR144 impaired human erythroid differentiation, unlike in zebrafish and mouse studies where the functional effect of MIR144 on erythropoiesis was minimal. In this study, we found RAB14 is a direct target of both MIR144 and MIR451. As MIR144 and MIR451 expression increased during human erythropoiesis, RAB14 protein expression decreased. Enforced RAB14 expression phenocopied the effect of MIR144 and/or MIR451 depletion, whereas shRNA-mediated RAB14 knockdown protected cells from MIR144 and/or MIR451 depletion-mediated erythropoietic inhibition. RAB14 knockdown increased the frequency and number of erythroid cells, increased β-haemoglobin expression, and decreased CBFA2T3 expression during human erythropoiesis. In summary, we utilized MIR144 and MIR451 to identify RAB14 as a novel physiological inhibitor of human erythropoiesis.
登录
查看更多内容
DOI：
10.1016/j.mrfmmm.2008.07.014
发表时间：
2008-12-01
影响因子：
2.3
作者：
Kiefer, Christine M.;Hou, Chunhui;Little, Jane A.;Dean, Ann
通讯作者：
Dean, Ann
影响因子：
3.8
作者：
Li Y;Bai H;Zhang Z;Li W;Dong L;Wei X;Ma Y;Zhang J;Yu J;Sun G;Wang F
通讯作者：
Wang F
影响因子：
2.6
作者：
Choong, Meng Ling;Yang, Henry He;McNiece, Ian
通讯作者：
McNiece, Ian
小 Rab GTPase Rab7b 通过增强 IL-6 产生和 STAT3-GATA-1 关联促进巨核细胞分化
影响因子：
4.7
作者：
He, Donghua;Chen, Taoyong;Cai, Zhen
通讯作者：
Cai, Zhen
影响因子：
3.2
作者：
Garzon, Ramiro;Croce, Carlo M.
通讯作者：
Croce, Carlo M.