Mir-1271及RTEF-1在青年及老年胃癌中的表达及意义

发布时间：2018-05-25 08:00

本文选题：mir-1271 + RTEF-1　；参考：《郑州大学》2015年硕士论文

【摘要】：背景与目的胃癌是我国胃肠道肿瘤中常见的恶性肿瘤,具有恶性程度高、易转移和死亡率高的特点。因此,深入研究胃癌发病的机制从而寻找到新的早期诊断和有效的治疗方法,是摆放在我国医疗工作者面前的重要问题。胃癌发病率随患者年龄增加而升高,其发病高峰年龄为60岁左右。较之青年胃癌,老年胃癌患者表现出组织学分化程度高、生物学侵袭性弱、肿瘤恶性程度低的临床特点。老年胃癌与青年胃癌在生物学行为上的这种差别提示两组胃癌在各自的发病及发展过程中存在着不同的分子调节机制。但是,目前尚不清楚是什么分子机制导致了老年胃癌具有相对低危的生物学特性。因此,研究老年和青年胃癌间存在的不同分子调节机制,有利于我们进一步深入了解胃癌发生、发展的过程,对于胃癌的个体化预防和治疗具有重要的理论指导意义。恶性肿瘤普遍具有高度异质性的特点,既往研究结果显示:老年胃癌是胃癌患者中的一个主要患者群体,其临床病理特征不同于青年胃癌,反映在:女性发病率显著低、组织学分化程度高、生物学侵袭性弱、肿瘤恶性度低等。且老年胃癌遗传倾向低于青年胃癌,表现为有胃癌家族史的患者明显较青年胃癌组低。分子学水平上,既往研究也发现老年胃癌及青年胃癌患者间的基因组谱差异,另外介导细胞黏附和维持细胞骨架的E-钙黏素和β-Catein表达水平和标志着DNA错配修复功能缺陷的微卫星不稳定性(MSI)等也在两组胃癌间存在着明显的差异。但是,前期的研究多止步于观察到上述差异,而缺少对其内在精确分子机制的研究。RTEF-1(Related Transcriptional Enhancer Factor-1,转录增强因子-1相关基因)来自转录增强子家族(Transcriptional Enhancer Factor,TEF)。1996年Stewart等人从心肌细胞中首次成功克隆并编码,随后其家族的其他成员被不断发现。目前已知该家族成员包括四个:TEF-1,RTEF-1,DTEF-1和ETF,该家族拥有一个共同的高度保守的DNA结合域,可以结合到基因启动子M-CAT原件上发挥其调节作用。RTEF-1作为转录增强子家族重要的组成部分,既往的研究多集中于其在内皮细胞和血管生成中的调节作用。Che P等人既往的研究结果证实了Mir-125a-5p通过下调RTEF-1可以导致老年小鼠血管生成障碍。鉴于血管生成和肿瘤的密切关系,近来RTEF-1在肿瘤形成中的作用同样引起了关注。我们提出假设:RTEF-1及相关调控因子在老年胃癌及青年胃癌中的表达是否存在差异,这种差异是否与老年胃癌和青年胃癌间的组织学分化程度、生物学侵袭性及肿瘤恶性程度的不同有关。目的:探讨RTEF-1及其上游调控基因在老年胃癌及青年胃癌中的表达是否存在差异及其意义。材料与方法1.研究对象及标本采集:标本采集于郑州大学第一附属医院胃肠外科2014年7月至2015年1月期间进行胃癌根治术的患者。纳入标准:术前胃镜病理提示为胃恶性肿瘤,计算机断层扫描(computed tomography,CT)等检查进行术前分期,提示患者可以行标准胃癌根治术,术后病理证实为胃癌中的低分化腺癌,术前未进行化疗,放疗及中西医结合等抗肿瘤治疗。本实验经我院道德伦理委员会的批准,而且经过患者知情同意并签署知情同意书。2.自Microarray数据结果中分析老年胃癌和青年胃癌中存在差异表达的mi RNAs;发现在老年胃癌及青年胃癌中表达存在明显差异的mi RNA,RT-q PCR验证;3.分别采用RT-q PCR、Western Blot技术检测RTEF-1在老年胃癌及青年胃癌原代细胞中的m RNA蛋白水平表达并进行比较。4.所有实验结果数据均采用SPSS17.0软件进行分析。以P0.05作为差异有统计学意义的检验标准。结果1.mir-1271在老年胃癌和青年胃癌中均含量丰富且变化相对明显;2.老年胃癌细胞中RTEF-1蛋白表达较青年胃癌减少;3.老年胃癌细胞中mir-1271表达是青年胃癌的3.2倍;结论老年胃癌及青年胃癌中mir-1271及RTEF-1存在差异性表达,这种差异可能是导致老年胃癌及青年胃癌在组织学分化程度、生物学侵袭性及肿瘤恶性程度存在差异的重要分子机制。
[Abstract]:Background and objective gastric cancer is a common malignant tumor of the gastrointestinal tract in China. It has the characteristics of high malignancy, easy transfer and high mortality. Therefore, it is an important problem placed in front of the medical workers in our country to study the pathogenesis of gastric cancer so as to find a new early diagnosis and effective treatment method. The age of the patients increased and the peak age was about 60 years old. Compared with the young gastric cancer, the elderly patients with gastric cancer showed high histological differentiation, weak biological invasiveness and low malignancy. This difference in biological behavior between the aged and the young gastric cancer suggests that the two groups of gastric cancer are in their respective pathogenesis and hair. There are different molecular mechanisms in the process. However, it is not clear what molecular mechanism leads to the relatively low risk of biological characteristics in elderly gastric cancer. Therefore, the study of different molecular mechanisms in the elderly and young gastric cancer is helpful for us to further understand the occurrence and development of gastric cancer and to the stomach. The individualized prevention and treatment of cancer have important theoretical guiding significance. The malignant tumor has the characteristics of high heterogeneity. The previous research results show that the elderly gastric cancer is a major group of patients with gastric cancer, whose clinicopathological features are different from those of young gastric cancer, which are reflected in the low incidence of female and high degree of histological differentiation. The genetic tendency of the old gastric cancer is lower than that of the young gastric cancer, and the patients with the family history of gastric cancer are obviously lower than those of the young gastric cancer group. The expression level of E- calcarin and beta -Catein and the microsatellite instability (MSI) indicating the functional defect of DNA mismatch repair (MSI) were also significantly different between the two groups of gastric cancers. However, the previous study stopped to observe the above differences, but there was a lack of.RTEF-1 (Related Transcriptional Enhancer) for its intrinsic precise molecular mechanism. Factor-1, -1 related genes from the transcription enhancer family (Transcriptional Enhancer Factor, TEF).1996 Stewart et al. Stewart et al. The first successful cloning and encoding from the cardiac myocytes, and then the other members of the family are constantly discovered. Now the family members are known to include four: TEF-1, RTEF-1, DTEF-1 and ETF, the family embraced There is a common highly conservative DNA binding domain that can be combined with the gene promoter M-CAT to play its regulatory role.RTEF-1 as an important component of the transcription enhancer family. Previous studies have concentrated on its regulatory role in endothelial cells and angiogenesis, and the previous results of.Che P, et al., confirmed that Mir-125a-5p Down regulation of RTEF-1 can lead to angiogenic disorders in old mice. In view of the close relationship between angiogenesis and tumor, the recent role of RTEF-1 in tumor formation is also concerned. We hypothesized: whether there is a difference in the expression of RTEF-1 and related regulatory factors in old and young gastric cancer, whether this difference is with the elderly Histological differentiation, biological invasiveness and tumor malignancy of gastric cancer and young gastric cancer. Objective: To investigate whether the expression of RTEF-1 and its upstream regulatory genes in old gastric cancer and young gastric cancer are different and its significance. Materials and methods 1. research objects and specimen collection: specimen collection at the first of Zhengzhou University Patients undergoing radical gastrectomy for gastric cancer from July 2014 to January 2015 of the affiliated hospital were included in the criteria: preoperative gastroscopic pathological hints for gastric malignant tumor, computed tomography (computed tomography, CT) and other examinations for preoperative staging, suggesting that patients can be treated with standard radical gastrectomy, and the postoperative pathology proved to be a low score in gastric cancer. Adenocarcinoma, chemotherapy, radiotherapy and combination of traditional Chinese and Western medicine were not performed before operation. This experiment was approved by the ethics committee of our hospital, and after the informed consent of the patients and the signing of the informed consent form.2. from the Microarray data, the differential expression of MI RNAs in old gastric cancer and young gastric cancer was analyzed, and it was found in old gastric cancer and Mi RNA, RT-q PCR, and RT-q PCR, Western Blot technology were used to detect the expression of M RNA protein in old gastric cancer and young gastric cancer cells by RT-q PCR and Western Blot, respectively, and the results of all experimental data were analyzed. Results 1.mir-1271 was rich in both old and young gastric cancer. The expression of RTEF-1 protein in 2. elderly gastric cancer cells was less than that in young gastric cancer, and the expression of mir-1271 in 3. old gastric cancer cells was 3.2 times as high as that of young gastric cancer. Conclusion there were differences in mir-1271 and RTEF-1 in old gastric cancer and young gastric cancer. Sexual expression, which may be an important molecular mechanism that leads to differences in histological differentiation, biological invasiveness and malignancy of old and young gastric cancer.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.2

【相似文献】