兰州大学机构库 >生命科学学院
X射线对胃癌miRNA表达谱的研究
Alternative TitleX-ray radiation alters miRNA expression profile in gastric cancer
何进鹏
Thesis Advisor谢小冬 ; 周光明
2010-05-25
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
KeywordmicroRNA 胃癌 X-射线 DNA损伤
Abstract在中国胃癌发病率与死亡率居各类恶性肿瘤之首。由于检测技术的局限性胃癌患者在就诊时多数已是中晚期,单纯手术治疗效果往往不理想,大多肿瘤细胞对化疗药物的耐受性又影响了化疗的效果。因此,开辟诊断和治疗胃癌的新途径迫在眉睫。目前,已有报道证实放疗辅助手术治疗可以显著增强胃癌治疗效果。microRNA(miRNA)是一类长度为19-25nt的非编码性内源单链小RNA,参与调控多种细胞活动,某些miRNA发挥着致癌或抑癌作用,在很多癌症中miRNA表达异常。此外,miRNA可参与细胞的多种应激反应,因此我们推测:miRNA可能作为一种新的标签分子用于胃癌早期诊断,另外,miRNA可能参与胃癌细胞的辐射应激调控。到目前为止,有关miRNA和胃癌细胞辐射应激响应的关系尚未见报道。本研究中,我们采用microRNA芯片技术,一方面检测了胃癌组织样与其对应正常胃组织样miRNA表达谱差异,获得了在胃癌中表达异常的miRNAs;另一方面,研究了X-射线辐照对胃癌组织miRNA表达的影响,胃癌组织样本经X-射线辐照(剂量为4Gy)后,通过miRNA芯片技术检测胃癌组织、X-射线辐照后胃癌组织miRNA表达谱,得到辐射胃癌组织内表达发生变化的miRNA。通过聚类分析对差异表达miRNA进行分类,选取在胃癌中表达上调但经X-射线辐照后表达下调到正常水平的miR-300在十份辐射胃癌组织中进行qRT-PCR定量检测,最后利用miRNA数据库对miR-300的靶基因进行预测。结果显示,在胃癌中有包括let-7e、miR-300在内的17种miRNA表达上调,而miR-30a、miR-138等9种miRNA表达下调;胃癌组织经过X-射线辐照后,let-7a、miR-300等16种miRNA表达下调,而辐射所致表达下调的16种miRNA中的7种是在胃癌中表达上调的。在受照射的10份胃癌组织中,有6份样本的miR-300表达明显下调。数据库预测显示miR-300可能调控包括CASP8AP2 、BCL2L11、CCNK等在细胞凋亡、细胞周期、DNA损伤修复等重要细胞进程中发挥重要作用的基因。总之,我们的实验证实了miR-300在胃癌内表达上调,X-射线辐射可显著降低miR-300在胃癌内的表达,miR-300潜在靶基因在多种重要细胞进程中发挥关键作用。
Other AbstractGastric cancer is the most common cancer in China, the incidence and mortality rate of gastric cancer ranks first in all kind of malignant tumors. Until now, surgical operation is the most important way to treat gastric cancer. However, limited by diagnostic method, most of the therapy can not be cured completely because of optimal cure time losing. Furthermore, multidrug resistance of cancer cells also affected the use of chemotherapy. Thus, it is quite necessary to find a new way to diagnose and cure gastric cancer. Now, it has been reported that it is markedly enhanced the effect by surgery accompanied with radiotherapy.microRNA (miRNA) is a new class of endogenous non-coding small RNAs with 19-25nt length. miRNA regulates various cell processes, and aberrant expression of some miRNAs in cancers implies that they act as oncogenes or tumor suppressor genes. Furthermore,miRNA is concerning with numbers of cell stress reaction. Thus, we postulated that miRNA might be a kind of new biomarker for early-stage gastric cancer diagnosis and included in gastric cancer cell radiation response. Until now, there has been no report on the potential roles of miRNA in gastric cancer cell radiation response.In this study, we compared the miRNA expression profiles between gastric cancer tissues and the corresponding gastric normal tissues with miRNA microarray. On the other hand, the effects of the X-ray irradiation on gastric cancer miRNA expression were studied. The results showed that 17 miRNAs including let-7 and miR-300 were over-expressed while 9 miRNAs were down-regulated. Upon irradiation with 4 Gy of X-ray, 7 miRNAs out of 16 miRNAs were up-regulated in gastric cancer were down-regulated. The miRNAs with changed expression level were classified 3 categories basing on the results of cluster analysis, among which miR-300 was chosen for further studies. 6 out of 10 irradiated gastric cancer tissues were found to have suppressed expression of miR-300 by using real-time RT-PCR. Putative target genes of miR-300 as predicted in miRBase are key factors playing important roles in varieties of cell progresses including apoptosis, cell cycle regulation, and DNA repair. So it suggested that miR-300 plays important roles in gastric cancer cell radiation response.In summary, our results demonstrated that miR-300 expression level was significantly increased in gastric cancer,while its expression was suppressed by X-ray dramatically。Moreover,the putative target genes of...
URL查看原文
Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/221828
Collection生命科学学院
Recommended Citation
GB/T 7714
何进鹏. X射线对胃癌miRNA表达谱的研究[D]. 兰州. 兰州大学,2010.
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