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首頁> 外文學(xué)位 >Deciphering the role of microRNA-708 in precursor B-cell acute lymphoblastic leukemia biology.
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Deciphering the role of microRNA-708 in precursor B-cell acute lymphoblastic leukemia biology.

機(jī)譯：解讀microRNA-708在前體B細(xì)胞急性淋巴細(xì)胞白血病生物學(xué)中的作用。

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摘要

MicroRNAs (miRs) are known to play major roles in both normal hematopoietic differentiation, as well as hematopoietic malignancies. In this work, we report that miR-708; a little studied miR, is up-regulated in most B-cell acute lymphoblastic leukemia (B-ALL) cell lines and primary patient samples compared to hematopoietic stem-progenitor cells (HSPCs) and mature healthy B-cells. Our first hypothesis in this regard was that miR-708 has an oncogene-like function in B-ALL biology. To test this hypothesis, we performed loss/gain of function assays to examine effect of miR-708 modulation on B-ALL cell proliferation. While overexpression of miR-708 failed to alter cell proliferation rate, knock-down of this miR conferred a growth disadvantage on B-ALL cell proliferation. Our second hypothesis was that accumulation of non-functional immature B cells in B-ALL is due to deregulated expression of miR-708 during B cell development. To test this hypothesis, we overexpressed miR-708 in donor murine hematopoietic progenitor (Lin-) cells and monitored their hematopoietic differentiation in recipient mice following bone marrow transplantation. Post transplantation, we failed to observe any influence of miR-708 on hematopoietic differentiation of Lin- cells. In addition, we also observed a positive correlation that exists between expression pattern of miR-708 and its host gene OdZ4. Hence, we hypothesize that up-regulated miR-708 could be a passenger of up-regulated OdZ4 in B-ALL. To test this hypothesis, we are currently examining effects of OdZ4 knock-down on B-ALL cell proliferation. In future we also propose to examine if miR-708 cooperates with OdZ4 function in B-ALL. Future work also needs to address if miR-708 affects oncogenic processes, other than growth, that could be involved in B-ALL biology.
機(jī)譯：已知MicroRNA（miR）在正常的造血分化以及造血系統(tǒng)惡性腫瘤中起主要作用。在這項(xiàng)工作中，我們報(bào)告了miR-708；與造血干祖細(xì)胞（HSPC）和成熟健康的B細(xì)胞相比，在大多數(shù)B細(xì)胞急性淋巴細(xì)胞白血?。˙-ALL）細(xì)胞系和原發(fā)性患者樣本中，經(jīng)過少量研究的miR上調(diào)。在這方面，我們的第一個假設(shè)是miR-708在B-ALL生物學(xué)中具有癌基因樣功能。為了檢驗(yàn)該假設(shè)，我們進(jìn)行了功能喪失/獲得功能分析以檢查miR-708調(diào)節(jié)對B-ALL細(xì)胞增殖的影響。盡管miR-708的過表達(dá)不能改變細(xì)胞增殖速率，但敲低該miR卻給B-ALL細(xì)胞增殖帶來了不利的生長。我們的第二個假設(shè)是B-ALL中非功能性未成熟B細(xì)胞的積累是由于B細(xì)胞發(fā)育過程中miR-708的表達(dá)失調(diào)所致。為了驗(yàn)證這一假設(shè)，我們在骨髓移植后的供體小鼠造血祖細(xì)胞（Lin-）中過表達(dá)了miR-708，并監(jiān)測了它們在造血干細(xì)胞中的分化。移植后，我們未能觀察到miR-708對Lin細(xì)胞的造血分化的任何影響。此外，我們還觀察到miR-708的表達(dá)模式與其宿主基因OdZ4之間存在正相關(guān)。因此，我們假設(shè)miR-708上調(diào)可能是B-ALL中OdZ4上調(diào)的乘客。為了檢驗(yàn)這個假設(shè)，我們目前正在研究OdZ4敲低對B-ALL細(xì)胞增殖的影響。將來，我們還建議檢查miR-708是否與B-ALL中的OdZ4功能配合使用。未來的工作還需要解決，miR-708是否會影響除B-ALL生物學(xué)以外的致癌過程（除了生長）。

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  • 作者

    Doshi, Kshama.;

  • 作者單位

    University of Maryland, Baltimore.;

  • 授予單位 University of Maryland, Baltimore.;
  • 學(xué)科 Biology Molecular.;Health Sciences Oncology.
  • 學(xué)位 M.S.
  • 年度 2012
  • 頁碼 60 p.
  • 總頁數(shù) 60
  • 原文格式 PDF
  • 正文語種 eng
  • 中圖分類 地球物理學(xué);
  • 關(guān)鍵詞

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