siRNA对HL-60细胞凋亡及c-Myc蛋白表达的影响
摘要
目的：
RNA干扰(RNA interference，RNAi)是新近发展起来的一种封闭基因表达的有效方法，是在mRNA水平上由内源性或外源性双链RNA(double-stranded RNA，dsRNA)诱发的高度特异的基因沉默机制。RNAi的基本原理是将与目的基因同源的含21～23个核苷酸的小分子干扰RNA(small interfering RNA，siRNA)转染至靶细胞，与细胞内的一系列特异性蛋白形成RNA诱导沉默复合体(RNA induced silencing complex，RISC)，RISC以siRNA为模板特异地识别其同源性靶mRNA分子并对其进行递进式剪切，形成强有效的瀑布效应，诱导序列特异性的mRNA降解，从而导致该基因表达下降。RNAi技术目前已广泛应用于基因治疗的研究。由于siRNA的高稳定性及高效特异的沉默诱导效应，siRNA对其靶基因所编码的蛋白表达的抑制效应优于传统的反义核酸技术。因此将siRNA应用于白血病的研究可能为白血病的治疗另辟蹊径。
原癌基因c-myc是myc家族的重要成员，其产物属核蛋白类的磷酸化蛋白质，在正常的细胞增殖、分化及凋亡过程中起重要作用。c-myc原癌基因在多种人类肿瘤细胞中均有扩增和高表达，在HL-60细胞株和白血病病人细胞中同样存在高表达现象。研究表明：用反义寡核苷酸技术和RNAi技术均可封闭c-myc癌基因的异常表达，并能抑制细胞增殖、诱导细胞凋亡。本试验选择高表达c-myc的HL-60细胞作为研究对象，合成靶向c-myc mRNA的siRNA，并将其导入HL-60细胞，观察其对HL-50细胞生长的抑制和c-Myc蛋白表达的影响，进一步通过DNA电泳及流式细胞术，研究该siRNA对HL-50细胞凋亡的影响，为c-myc siRNA作为基因药物治疗白血病提供理论依据。
方法：
Aim:
RNA interference (RNAi) which recently developed is an effective method to inhibit gene expression。 It is in the mRNA level that endogenic or exogenic double- strand RNA (dsRNA) induces gene silencing with high specifity. The basic principle is to transfect cells with small interfering RNA(siRNA) containing 21 ~ 23 nucleotides homologous in sequence to the target gene. siRNA and a series of specific proteins in cells form RISC (RNA induced silencing complex). RISC taking siRNA as its template specially binds to homologous mRNA and progressively cuts the mRNA, forming strongly effective waterfall effects and inducing sequence-specific mRNA degeneration. As a result, the target gene is silenced. siRNA has been extensively applied to the research of gene therapy. Because siRNA has a high stability, speciality and efficacy in inducing gene silence, it is superior to antisense oligonuleotides in reducing protein expression coded by target mRNA. Applying siRNA to leukemia therapy may make a new way in the treatment of leukemia.
Oncogene c-myc is an important member in the myc family, and the phosphate-protein encoded by this gene belongs to nucleoprotein. It plays a vital role in the process of proliferation, differentiation and apoptosis of normal cells. The c-myc gene has a high level expression in many kinds of human tumor cells, as well as in HL-60 cells
RNA干扰(RNA interference，RNAi)是新近发展起来的一种封闭基因表达的有效方法，是在mRNA水平上由内源性或外源性双链RNA(double-stranded RNA，dsRNA)诱发的高度特异的基因沉默机制。RNAi的基本原理是将与目的基因同源的含21～23个核苷酸的小分子干扰RNA(small interfering RNA，siRNA)转染至靶细胞，与细胞内的一系列特异性蛋白形成RNA诱导沉默复合体(RNA induced silencing complex，RISC)，RISC以siRNA为模板特异地识别其同源性靶mRNA分子并对其进行递进式剪切，形成强有效的瀑布效应，诱导序列特异性的mRNA降解，从而导致该基因表达下降。RNAi技术目前已广泛应用于基因治疗的研究。由于siRNA的高稳定性及高效特异的沉默诱导效应，siRNA对其靶基因所编码的蛋白表达的抑制效应优于传统的反义核酸技术。因此将siRNA应用于白血病的研究可能为白血病的治疗另辟蹊径。
原癌基因c-myc是myc家族的重要成员，其产物属核蛋白类的磷酸化蛋白质，在正常的细胞增殖、分化及凋亡过程中起重要作用。c-myc原癌基因在多种人类肿瘤细胞中均有扩增和高表达，在HL-60细胞株和白血病病人细胞中同样存在高表达现象。研究表明：用反义寡核苷酸技术和RNAi技术均可封闭c-myc癌基因的异常表达，并能抑制细胞增殖、诱导细胞凋亡。本试验选择高表达c-myc的HL-60细胞作为研究对象，合成靶向c-myc mRNA的siRNA，并将其导入HL-60细胞，观察其对HL-50细胞生长的抑制和c-Myc蛋白表达的影响，进一步通过DNA电泳及流式细胞术，研究该siRNA对HL-50细胞凋亡的影响，为c-myc siRNA作为基因药物治疗白血病提供理论依据。
方法：
Aim:
RNA interference (RNAi) which recently developed is an effective method to inhibit gene expression。 It is in the mRNA level that endogenic or exogenic double- strand RNA (dsRNA) induces gene silencing with high specifity. The basic principle is to transfect cells with small interfering RNA(siRNA) containing 21 ~ 23 nucleotides homologous in sequence to the target gene. siRNA and a series of specific proteins in cells form RISC (RNA induced silencing complex). RISC taking siRNA as its template specially binds to homologous mRNA and progressively cuts the mRNA, forming strongly effective waterfall effects and inducing sequence-specific mRNA degeneration. As a result, the target gene is silenced. siRNA has been extensively applied to the research of gene therapy. Because siRNA has a high stability, speciality and efficacy in inducing gene silence, it is superior to antisense oligonuleotides in reducing protein expression coded by target mRNA. Applying siRNA to leukemia therapy may make a new way in the treatment of leukemia.
Oncogene c-myc is an important member in the myc family, and the phosphate-protein encoded by this gene belongs to nucleoprotein. It plays a vital role in the process of proliferation, differentiation and apoptosis of normal cells. The c-myc gene has a high level expression in many kinds of human tumor cells, as well as in HL-60 cells
引文
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56．王方金，吴健，王伟毅等，运用siRNA抑制K562细胞中端粒酶逆转录酶基因表达的研究，临床内科杂志，2005 5；22(5)：330-332。
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58．王方金，何蕴韶。应用siRNA抑制K562细胞中c-myc基因的表达。解剖学研究，2005，27(1)：12-18
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