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  本文選題：miR-638 + 自噬�。� 參考：《北京化工大學(xué)》2016年博士論文

【摘要】：非編碼RNA近來一直是腫瘤學(xué)的研究熱點(diǎn),其在細(xì)胞生長、細(xì)胞調(diào)亡及各種代謝途徑都具有調(diào)控作用。非編碼RNA從長度上來劃分可以分為3類:小于50nt、50nt到500nt、大于500nt。本課題以小于50nt的微小非編碼RNA (miR-638)和大于500nt的長鏈非編碼RNA (MEG3)為研究對象,研究了 miR-638對腫瘤細(xì)胞自噬的調(diào)控和機(jī)制,以及MEG3對肝癌細(xì)胞生長的影響。微小RNA是一類調(diào)控性非編碼RNA,參與胚胎發(fā)育、腫瘤發(fā)生等眾多生理和病理過程,近年研究顯示微小RNA也是重要的自噬調(diào)控因子。自噬不僅可以調(diào)控細(xì)胞生長、分化以及維持內(nèi)環(huán)境穩(wěn)態(tài)等生物學(xué)行為,而且在腫瘤發(fā)生與演進(jìn)過程中亦發(fā)揮重要作用。本課題研究發(fā)現(xiàn)miR-638通過抑制靶基因DACT3的表達(dá)促進(jìn)食管鱗癌KYSE450細(xì)胞和乳腺癌MCF-7細(xì)胞自噬。同時,通過對細(xì)胞進(jìn)行臺盼藍(lán)計數(shù)生長測定、劃痕愈合實驗及Transwell實驗證明miR-638可以顯著促進(jìn)細(xì)胞的增殖、遷移和侵襲。miRNA-自噬調(diào)控紊亂可能是腫瘤及其它疾病過程中重要的分子事件,本研究將為闡明腫瘤等疾病過過程的發(fā)病機(jī)制及為探索新的治療策略提供新思路。越來越多的研究表明長鏈非編碼RNA(lncRNAs)在癌癥生物學(xué)方面扮演非常重要的角色,在癌癥的治療方面表現(xiàn)出很大的潛力。本課題研究中的MEG3和正常組織比起來在癌組織中低表達(dá)或不表達(dá),但可以調(diào)節(jié)P53靶基因的表達(dá),和P53相互作用來抑制腫瘤細(xì)胞的增殖。我們篩選出一種肝靶向陽離子聚合物PuPGEA2,它可以和MEG3與P53形成納米復(fù)合物 PuPGEA2/MEG3, PuPGEA2/P53 或 PuPGEA2/(MEG3+P53),能有效地抑制肝癌細(xì)胞的增殖,研究結(jié)果表明lncRNA可作為肝癌診斷、治療、預(yù)后判斷的新靶點(diǎn)。
[Abstract]:Noncoding RNA has been a hot topic in oncology recently. It plays a regulatory role in cell growth, cell apoptosis and various metabolic pathways.The non-coding RNA can be divided into three categories in terms of length: less than 50 NT to 500 NT and greater than 500 NT.In this study, the regulation and mechanism of miR-638 on autophagy and the effect of MEG3 on the growth of hepatoma cells were studied, which were smaller than 50nt (RNA miR-638) and longer chain uncoded RNA (MEG3) than 500nt.MicroRNAs are a class of non-coding regulatory RNAs involved in many physiological and pathological processes such as embryonic development and tumorigenesis. Recent studies have shown that microRNAs are also important autophagy regulators.Autophagy not only regulates cell growth, differentiation and homeostasis, but also plays an important role in tumorigenesis and progression.In this study, we found that miR-638 promoted autophagy of esophageal squamous cell carcinoma KYSE450 cells and breast cancer MCF-7 cells by inhibiting the expression of target gene DACT3.At the same time, the cell growth was determined by trypan blue count, scratch healing test and Transwell test showed that miR-638 can significantly promote the proliferation of cells.Migration and invasion. MiRNA-autophagy regulation disorder may be an important molecular event in the process of tumor and other diseases. This study will provide new ideas for elucidating the pathogenesis of tumor and other diseases and exploring new treatment strategies.A growing number of studies have shown that long chain noncoding RNAs lncRNAss play a very important role in cancer biology and have great potential in the treatment of cancer.Compared with normal tissues, MEG3 in this study is low or not expressed in cancer tissues, but it can regulate the expression of p53 target gene and interact with p53 to inhibit the proliferation of tumor cells.We have screened out a liver-targeted cationic polymer PuPGEA2, which can form a nano-complex PuPGEA2 / MEG3, PuPGEA2/P53 or PuPGEA2/(MEG3 P53 with MEG3 and p53, which can effectively inhibit the proliferation of hepatoma cells. The results show that lncRNA can be used as a diagnosis and therapy for HCC.A new target for prognostic judgment.
【學(xué)位授予單位】：北京化工大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R735.7

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 李淵成;韋嘉勵;金由辛;;MiRNA對自噬的調(diào)控及在癌癥中的作用[J];生命的化學(xué);2015年03期

2 史華俊;劉忠;郭俊明;;非編碼長鏈RNA與基因表達(dá)調(diào)控[J];中國生物化學(xué)與分子生物學(xué)報;2012年09期

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本文編號：1740691