转录诱导的嵌合RNAs在前列腺癌中的作用

发布时间：2018-03-31 17:33

本文选题：转录　切入点：诱导　出处：《浙江大学》2014年硕士论文

【摘要】：目的前列腺癌的发病率在西方国家位于男性恶性肿瘤首位,而我国该病发病率近年来也显著上升,前列腺癌有着明显的种族特异性,产生这种特异性的分子生物学机制至今未明。基因融合是前列癌发生发展的重要遗传基础。Cell Rearch报道了四个发生频率很高的中国人群特异的融合基因USP9Y-TTTY15(19/54)、 RAD50-PDLIM4(15/54)、CTAGE5-KHDRBS3(20/54)、SDK1-AMACR(13/54)。我们的研究目的是证实USP9Y-TTTY15、RAD50-PDLIM4在过人群中的存在,进而说明东西方发病率的差异。方法通过RT-PCR及FISH的方法确认其中两个融合基因的存在,对本院105例前列腺癌新鲜样本进行上述两个融合基因及其它相关基因进行研究,经过反复验证,没有发现上述RAD50-PDLIM4融合基因,但发现有USP9Y-TTTY15及SLC45A3-ELK4融合基因；然后对这些融合基因与Gleason评分、TNM、PSA、年龄、是否有转移等的关系进行分析。通过定量PCR还分析了USP9Y-TTTY15与SLC45A3-ELK4在105对前列腺癌组织和正常组织中的表达水平, 结果USP9Y-TTTY15在前列腺癌组织、正常前列腺组织和其他正常组织(肺、胆囊、肾)中都存在,USP9Y-TTTY15是在前列腺癌和正常组织中存在的转录诱导嵌合RNAs。有研究分析转录诱导嵌合RNA SLC45A3-ELK4与前列腺癌的进展相关联。通过定量PCR还发现USP9Y-TTTY15和嵌合RNA SLC45A3-ELK4在癌组织和正常组织中表达差异很大,癌组织中USP9Y-TTTY15并不比正常组织高,与高级别的前列腺癌也没有关联。同时我们发现：与正常组织相比,SLC45A3-ELK4表达水平在癌组织中较高,只有当SLC45A3-ELK4在癌组织中的表达量明显高于正常组织的表达量时(10倍),SLC45A3-ELK4表达水平与前列腺癌临床数据有关,包括高PSA水平,Gleason评分,临床分期,淋巴结转移等。而单独的前列腺癌症样本中SLC45A3-ELK4的表达水平与这些临床参数不相关。结论USP9Y-TTTY15是转录诱导的嵌合RNA, SLC45A3-ELK4在前列腺癌中的作用没有之前报道的那么大,转录诱导的嵌合RNA USP9Y-TTTY15与SLC45A3-ELK4在前列腺癌中的作用很小(P0.05)。因此,当一个新的融合基因被确定时,仔细检查癌组织和正常组织中嵌合RNAs的存在是必要的,
[Abstract]:Objective the incidence of prostate cancer is the highest in the western countries, and the incidence of prostate cancer in China has increased significantly in recent years. The incidence of prostate cancer has obvious race specificity. The molecular biological mechanism to produce this specificity is not clear. Gene fusion is an important genetic basis for the occurrence and development of cancer. Cell Rearch has reported four high frequency Chinese population specific fusion genes USP9Y-TTTY1515 / 54, RAD50-PDLIM415 / 54, CTAGE5-KHDRBS320 / 54 / SDK1-AMACRN 13 / 54. The purpose of the study was to confirm the presence of USP9Y-TTTY15 RAD50-PDLIM4 in the human population. Then explain the difference of incidence rate between East and West. Methods two of the fusion genes were confirmed by RT-PCR and FISH. The two fusion genes and other related genes were studied in 105 fresh samples of prostate cancer. No RAD50-PDLIM4 fusion genes were found, but USP9Y-TTTY15 and SLC45A3-ELK4 fusion genes were found. Quantitative PCR was also used to analyze the expression of USP9Y-TTTY15 and SLC45A3-ELK4 in prostate cancer tissues and normal tissues. Results USP9Y-TTTY15 was found in prostate cancer tissue, normal prostate tissue and other normal tissues (lung, gallbladder, gallbladder). USP9Y-TTTY15 is a transcription-induced chimeric RNAs in prostate cancer and normal tissues. Some studies have analyzed the association between transcription-induced chimeric RNA SLC45A3-ELK4 and the progression of prostate cancer. USP9Y-TTTY15 and chimeric RNA SLC45A3-ELK4 were also found in cancer by quantitative PCR. There is a big difference between tissue and normal tissue. USP9Y-TTTY15 was not higher in cancer tissues than in normal tissues and was not associated with high grade prostate cancer. We also found that the expression of SLC45A3-ELK4 was higher in cancer tissues than in normal tissues. Only when the expression of SLC45A3-ELK4 in cancer tissue was significantly higher than that in normal tissue was 10 times higher. The expression level of SLC45A3-ELK4 was related to the clinical data of prostate cancer, including high PSA level and Gleason score, clinical stage. Lymph node metastasis and so on. The expression of SLC45A3-ELK4 in individual prostate cancer samples was not correlated with these clinical parameters. Conclusion USP9Y-TTTY15 is a transcription-induced chimeric RNAs, and the role of SLC45A3-ELK4 in prostate cancer is not as great as previously reported. The role of transcription-induced chimeric RNA USP9Y-TTTY15 and SLC45A3-ELK4 in prostate cancer is very small (P0.05). Therefore, when a new fusion gene is identified, It is necessary to examine carefully the presence of chimeric RNAs in cancer and normal tissues.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.25

【共引文献】