长链非编码RNA在肾癌发生和发展过程中的作用及其临床意义

发布时间：2018-04-13 22:23

本文选题：长链非编码RNA + lncRNA　；参考：《中国人民解放军医学院》2017年硕士论文

【摘要】：第一部分长链非编码RNA-HRC在肾透明细胞癌中高表达并促进肿瘤细胞增殖和转移目的:越来越多的研究表明,长链非编码RNA (longnon-coding RNA,lncRNA)在癌症的发生发展中具有重要的作用。本文旨在阐明lncRNA NR_0243 73 (我们把它命名为 lncRNA HRC,即 a lncRNA which is Highly-expressed in Renal Cancer的缩写),在肾透明细胞癌中发生和转移中的作用。方法:用实时定量PCR的方法检测在60对肾透明细胞癌肿瘤及瘤旁组织、6株肾癌细胞系和一株正常肾小管上皮细胞系(HKC)中lncRNAHRC的表达水平。运用核浆分离实验检测lncRNAHRC在肾透明细胞癌细胞中的定位。运用siRNA方法在786-0细胞系中敲低lncRNAHRC的表达,运用慢病毒转染的方法在Caki-2细胞系中过表达lncRNA HRC,进一步检测lncRNAHRC对细胞周期、细胞增殖、细胞侵袭和转移能力的影响。结果:lncRNAHRC是一个长链基因间非编码RNA,其主要定位于细胞质,基因位点位于染色体2q13。在肾透明细胞癌肿瘤组织中表达为瘤旁组织的3.77倍(p0.001),在肾癌细胞系中也高表达。lncRNA-HRC的高表达与肿瘤大小(p=0.0056),Fuhrman分级(p=0.0002)、肿瘤分级(p0.0001)以及淋巴结转移(p=0.0384)密切相关。敲低lncRNA HRC抑制786-0细胞肿瘤增殖和转移,过表达lncRNA HRC促进Caki-2细胞肿瘤增殖和转移。结论:本研究首次报道了 lncRNAHRC在肾癌中的功能,通过临床病理资料及实验证实lncRNAHRC是一个细胞质转录RNA,在肾透明细胞癌中高表达,lncRNA HRC促进了肾癌细胞的增殖和转移,这表明lncRNA HRC有望成为肾透明细胞癌治疗的新的基因靶点。第二部分长链非编码RNA在肾癌中发挥预后和诊断价值的系统评价和meta分析目的:探究lncRNA在肾癌中的临床价值。方法:我们通过系统评价和meta分析的方法,从临床病理资料、预后及诊断等方面来研究长链非编码RNA(long noncoding RNA,lncRNA)在肾癌中的临床价值。结果:经过严格的筛选,最终纳入14项研究,其中包括10项临床病理资料研究,11项预后研究,3项诊断研究。结果表明 MALAT1 (metastasis-associated lung adenocarcinoma transcript 1)的表达与肿瘤分级相关(比值比[OR], 3.46; 95% 可信区间[CI],1.63-7.36,p=0.001),MALAT1的表达升高可以当作肾癌早期淋巴结转移的预测标记物,也可作为肾癌患者的独立预后因子,MALAT1越高,肾癌患者预后越差(总生存[OS];风险比[HR],2.97, 95%CI, 1.68-5.28; p0.001)。在诊断方面,合并的结果表明相较于其他肿瘤标记物,lncRNA在肾癌中具有高的敏感性(敏感度:0.89)和特异性(特异度:0.89),曲线下面积为0.94 (95% CI,0.92-0.96)。结论:本系统综述和meta分析表明lncRNA可以当作肾癌的肿瘤标记物来预测肿瘤的淋巴结转移和远处转移。LncRNA可作为肾癌的预后标记物,lncRNA在肾癌的诊断方面也具有较高的价值。
[Abstract]:Part I: long chain noncoding RNA-HRC is highly expressed in renal clear cell carcinoma and promotes tumor cell proliferation and metastasis. More and more studies have shown that long chain non coding RNA longnon-coding RNAs play an important role in carcinogenesis and progression.The purpose of this paper is to elucidate the role of lncRNA NR_0243 73 (we call it lncRNA HRC, or a lncRNA which is Highly-expressed in Renal Cancer) in the development and metastasis of renal clear cell carcinoma.Methods: real-time quantitative PCR was used to detect the expression of lncRNAHRC in 60 cases of renal clear cell carcinoma (RCC) and 6 renal cell carcinoma cell lines (RCC) and a normal renal tubular epithelial cell line (RTC).The localization of lncRNAHRC in renal clear cell carcinoma cells was detected by nuclear and cytoplasmic separation assay.SiRNA method was used to lower the expression of lncRNAHRC in 786-0 cell line, and lentivirus transfection was used to overexpression lncRNA HRC in Caki-2 cell line. The effects of lncRNAHRC on cell cycle, cell proliferation, cell invasion and metastasis were further examined.Results 1: lncRNAHRC is a long chain noncoding RNAs, mainly located in cytoplasm and located on chromosome 2q13.The high expression of .lncRNA-HRC in renal cell carcinoma cell line was closely related to the size of tumor p0.0056Fuhrman grade (0.0002), tumor grade (p0.0001) and lymph node metastasis (p0.0384).Knockdown of lncRNA HRC inhibited proliferation and metastasis of 786-0 cells, and overexpression of lncRNA HRC promoted proliferation and metastasis of Caki-2 cells.Conclusion: this study reports the function of lncRNAHRC in renal cell carcinoma for the first time. It is proved that lncRNAHRC is a cytoplasmic transcriptional RNAs by clinicopathological data and experiments. The overexpression of lncRNAHRC in renal clear cell carcinoma promotes the proliferation and metastasis of renal cancer cells.This suggests that lncRNA HRC may be a new gene target for the treatment of renal clear cell carcinoma.The second part: systematic evaluation and meta analysis of the prognostic and diagnostic value of long chain noncoding RNA in renal cell carcinoma objective: to explore the clinical value of lncRNA in renal cell carcinoma.Methods: by means of systematic evaluation and meta analysis, we studied the clinical value of long chain noncoding RNA(long noncoding RNA in renal cell carcinoma from the aspects of clinicopathological data, prognosis and diagnosis.Results: after strict screening, 14 studies were included, including 10 clinicopathological studies, 11 prognostic studies and 3 diagnostic studies.The results showed that the expression of MALAT1 metastasis-associated lung adenocarcinoma transcript 1 was correlated with the tumor grade (OR, 3.46; 95% CI). The increased expression of MALAT1 could be used as a predictor of early lymph node metastasis in renal cell carcinoma and as an independent prognostic factor of renal cell carcinoma.The worse prognosis was (total survival [OS]; risk ratio [HR] 2.97,95 CI, 1.68-5.28; p 0.001).In diagnosis, the combined results showed that LncRNA was more sensitive than other tumor markers in RCC (sensitivity: 0.89) and specificity (specificity: 0.89, area under the curve was 0.94 95% CI 0.92-0.96).Conclusion: this system review and meta analysis show that lncRNA can be used as a tumor marker to predict lymph node metastasis and distant metastasis of renal cell carcinoma. LncRNA can be used as a prognostic marker of renal cell carcinoma and has a high value in the diagnosis of renal cell carcinoma.
【学位授予单位】：中国人民解放军医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.11

【相似文献】