發(fā)布時間：2018-04-13 22:23

  本文選題：長鏈非編碼RNA + lncRNA��； 參考：《中國人民解放軍醫(yī)學(xué)院》2017年碩士論文

【摘要】：第一部分長鏈非編碼RNA-HRC在腎透明細(xì)胞癌中高表達(dá)并促進(jìn)腫瘤細(xì)胞增殖和轉(zhuǎn)移目的:越來越多的研究表明,長鏈非編碼RNA (longnon-coding RNA,lncRNA)在癌癥的發(fā)生發(fā)展中具有重要的作用。本文旨在闡明lncRNA NR_0243 73 (我們把它命名為 lncRNA HRC,即 a lncRNA which is Highly-expressed in Renal Cancer的縮寫),在腎透明細(xì)胞癌中發(fā)生和轉(zhuǎn)移中的作用。方法:用實時定量PCR的方法檢測在60對腎透明細(xì)胞癌腫瘤及瘤旁組織、6株腎癌細(xì)胞系和一株正常腎小管上皮細(xì)胞系(HKC)中l(wèi)ncRNAHRC的表達(dá)水平。運用核漿分離實驗檢測lncRNAHRC在腎透明細(xì)胞癌細(xì)胞中的定位。運用siRNA方法在786-0細(xì)胞系中敲低lncRNAHRC的表達(dá),運用慢病毒轉(zhuǎn)染的方法在Caki-2細(xì)胞系中過表達(dá)lncRNA HRC,進(jìn)一步檢測lncRNAHRC對細(xì)胞周期、細(xì)胞增殖、細(xì)胞侵襲和轉(zhuǎn)移能力的影響。結(jié)果:lncRNAHRC是一個長鏈基因間非編碼RNA,其主要定位于細(xì)胞質(zhì),基因位點位于染色體2q13。在腎透明細(xì)胞癌腫瘤組織中表達(dá)為瘤旁組織的3.77倍(p0.001),在腎癌細(xì)胞系中也高表達(dá)。lncRNA-HRC的高表達(dá)與腫瘤大小(p=0.0056),Fuhrman分級(p=0.0002)、腫瘤分級(p0.0001)以及淋巴結(jié)轉(zhuǎn)移(p=0.0384)密切相關(guān)。敲低lncRNA HRC抑制786-0細(xì)胞腫瘤增殖和轉(zhuǎn)移,過表達(dá)lncRNA HRC促進(jìn)Caki-2細(xì)胞腫瘤增殖和轉(zhuǎn)移。結(jié)論:本研究首次報道了 lncRNAHRC在腎癌中的功能,通過臨床病理資料及實驗證實lncRNAHRC是一個細(xì)胞質(zhì)轉(zhuǎn)錄RNA,在腎透明細(xì)胞癌中高表達(dá),lncRNA HRC促進(jìn)了腎癌細(xì)胞的增殖和轉(zhuǎn)移,這表明lncRNA HRC有望成為腎透明細(xì)胞癌治療的新的基因靶點。第二部分 長鏈非編碼RNA在腎癌中發(fā)揮預(yù)后和診斷價值的系統(tǒng)評價和meta分析目的:探究lncRNA在腎癌中的臨床價值。方法:我們通過系統(tǒng)評價和meta分析的方法,從臨床病理資料、預(yù)后及診斷等方面來研究長鏈非編碼RNA(long noncoding RNA,lncRNA)在腎癌中的臨床價值。結(jié)果:經(jīng)過嚴(yán)格的篩選,最終納入14項研究,其中包括10項臨床病理資料研究,11項預(yù)后研究,3項診斷研究。結(jié)果表明 MALAT1 (metastasis-associated lung adenocarcinoma transcript 1)的表達(dá)與腫瘤分級相關(guān)(比值比[OR], 3.46; 95% 可信區(qū)間[CI],1.63-7.36,p=0.001),MALAT1的表達(dá)升高可以當(dāng)作腎癌早期淋巴結(jié)轉(zhuǎn)移的預(yù)測標(biāo)記物,也可作為腎癌患者的獨立預(yù)后因子,MALAT1越高,腎癌患者預(yù)后越差(總生存[OS];風(fēng)險比[HR],2.97, 95%CI, 1.68-5.28; p0.001)。在診斷方面,合并的結(jié)果表明相較于其他腫瘤標(biāo)記物,lncRNA在腎癌中具有高的敏感性(敏感度:0.89)和特異性(特異度:0.89),曲線下面積為0.94 (95% CI,0.92-0.96)。結(jié)論:本系統(tǒng)綜述和meta分析表明lncRNA可以當(dāng)作腎癌的腫瘤標(biāo)記物來預(yù)測腫瘤的淋巴結(jié)轉(zhuǎn)移和遠(yuǎn)處轉(zhuǎn)移。LncRNA可作為腎癌的預(yù)后標(biāo)記物,lncRNA在腎癌的診斷方面也具有較高的價值。
[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.
【學(xué)位授予單位】：中國人民解放軍醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.11

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