c-Myb is an evolutionary conserved miR-150 target and miR-150/c-Myb interaction is important for embryonic development
c-Myb is an evolutionary conserved miR-150 target and miR-150/c-Myb interaction is important for embryonic development
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DOI：
10.1093/molbev/msn165
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发表时间：
2008-10-01
影响因子：
10.7
通讯作者：
Yu, Alice L.
中科院分区：
文献类型：
--
作者：
Lin, You-Chin;Kuo, Ming-Wei;Yu, Alice L.
人类c-Myb原癌基因在造血祖细胞以及白血病和某些实体瘤中高度表达。然而，其表达和生物学功能的调控机制仍不清楚。最近，已经显示c-MyB被microRNA-150（miR-150）靶向，从而控制小鼠中的B细胞分化。在这项研究中，我们证明了c-Myb是一个进化保守的目标，miR-150在人类和斑马鱼，使用报告分析。乳腺癌和白血病细胞中miR-150的异位表达在信使RNA（mRNA）和蛋白质水平上抑制了内源性c-Myb。在几种白血病细胞系、原代白血病细胞和正常淋巴细胞中，miR-150的表达水平与c-Myb呈负相关。斑马鱼受精卵中miR-150过表达或c-Myb沉默导致斑马鱼出现类似的严重表型缺陷，而c-Myb mRNA共注射可逆转miR-150诱导的表型畸变。我们的研究结果表明，c-Myb是miR-150的进化保守的目标和miR-150/c-Myb的相互作用是重要的胚胎发育和可能的肿瘤发生。
Human c-Myb proto-oncogene is highly expressed in hematopoietic progenitors as well as leukemia and certain solid tumor. However, the regulatory mechanisms of its expression and biological functions remain largely unclear. Recently, c-Myb has been shown to be targeted by microRNA-150 (miR-150) which thereby controls B cell differentiation in mice. In this study, we demonstrated that c-Myb is an evolutionary conserved target of miR-150 in human and zebrafish, using reporter assays. Ectopic expression of miR-150 in breast cancer and leukemic cells repressed endogenous c-Myb at both messenger RNA (mRNA) and protein levels. Among several leukemia cell lines, primary leukemia cells, and normal lymphocytes, expression levels of miR-150 inversely correlated with c-Myb. The miR-150 overexpression or c-Myb silencing in zebrafish zygotes led to similar and serious phenotypic defects in zebrafish, and the phenotypic aberrations induced by miR-150 could be reversed by coinjection of c-Myb mRNA. Our findings suggest that c-Myb is an evolutionally conserved target of miR-150 and miR-150/c-Myb interaction is important for embryonic development and possibly oncogenesis.