探討TPA誘導HL-60細胞分化的基因表現與微型核醣核酸之關係

Relationship between Gene Expression and microRNA in TPA-Induced HL-60 Cell Differentiation

倪國欽(Kuo-Chin Ni)

指導教授 ： 阮雪芬

國立臺灣大學/生命科學院/分子與細胞生物學研究所/碩士(2007年)

https://doi.org/10.6342/NTU.2007.02295

摘要

癌症促進劑12-鄰-四葵酸-佛波醇-13-乙酸(TPA)是人類前骨髓血癌(APL)細胞的潛在分化誘導劑。我們整合了cDNA微陣列技術與計算生物學來研究由TPA所誘導的HL-60細胞分化。近年來的研究指出微型核糖核酸(miRNA)能夠控制細胞分化、細胞生長、細胞發育，及細胞凋亡。而微型核糖核酸是一種大約22個核苷酸長度的內生性核糖核酸，可與對應基因的mRNA作用，導致mRNA的切除或造成轉錄抑制，進而抑制基因的表現。因此，為了了解這個調節機制，很重要的是必須找出與表現量差異的基因相關的miRNA。而我們開發的軟體，miLink，即能夠建立miRNA與基因表現的關係，而預測的結果，則可透過Q-PCR進一步驗證。藉由這個研究，我們連結了在人類前骨髓性細胞分化為巨噬細胞的過程中，miRNA與基因表現的關係，並提出一個在血癌治療中，具有重要性與深遠的影響。

關鍵字

TPA ； 急性前骨髓性血癌 ； HL-60 ； 微型核糖核酸

並列摘要

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) is a potent inducer in differentiation of human acute promyelocytic leukemia (APL) cells. We applied an approach integrating cDNA microarray and computational biology to study the differentiation of HL-60 cells induced by TPA. Recent evidences have shown that MciroRNAs (miRNAs) control differentiation, cell growth, development and apoptosis. MiRNAs are endogenous ~22-nt RNAs that repress gene expression by targeting mRNA for cleavage or translational repression. Hence, for understanding the regulatory mechanism, it’s critical to identify miRNAs correlated to the differential expressed genes. Our developed software, miLink, can provide the function in building the correlation between miRNAs and gene expression. The expression results of miRNAs were confirmed by real-time Q-PCR. This study provides a connection between gene expression and microRNA of human myeloid leukemia cells differentiation to macrophages and set forth a constructive far-reaching impact on leukemia therapy.

並列關鍵字

TPA ； acute promyelocytic leukemia (APL ) ； HL-60 ； microRNA

參考文獻

[124] 行政院衛生署，衛生統計資訊網.

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