本文選題：肝癌 + microRNA�。� 參考：《中國科學技術(shù)大學》2016年碩士論文

【摘要】：肝癌是世界上最常見的惡性腫瘤之一,一般發(fā)現(xiàn)的時候都是晚期且常規(guī)治療手段如切除、移植肝臟等效果十分有限,導致這種疾病沒有很好的治療療效,預后差。microRNA是一種短鏈非編碼RNA,通過靶向沉默靶基因行使轉(zhuǎn)錄后調(diào)控功能。越來越多的證據(jù)表明microRNA在肝臟的發(fā)育、再生、代謝過程中發(fā)揮著重要的調(diào)控作用。由于microRNA在腫瘤發(fā)生發(fā)展中基于病理反應(yīng)會發(fā)生微調(diào)作用,所以闡明microRNA失調(diào)造成的病理機制對于疾病的診斷和治療都非常有必要。我們在肝癌細胞系中分別轉(zhuǎn)染let-7f的mimics和抑制物,實驗結(jié)果反應(yīng)let-7f是一個抑癌基因。隨后使用生物信息學算法RNA22預測了let-7f的靶點為c-Met并且通過熒光素酶報告基因檢測及免疫印跡驗證。我們發(fā)現(xiàn)c-Met是let-7f的靶點,并且在肝癌的增殖轉(zhuǎn)移過程中起到促進作用。通過體外實驗,let-7f可以抑制肝癌細胞的增殖與轉(zhuǎn)移,這種作用可以部分地因恢復c-Met表達而逆轉(zhuǎn)。我們現(xiàn)在正在進行更深入的生物信息學分析,找到let-7f以及c-Met相關(guān)信號通路并且準備在體內(nèi)實驗中更深入地闡明let-7f低表達在肝癌發(fā)生發(fā)展中的作用。總的來說,我們通過體外實驗闡明了let-7f通過靶向抑制c-Met的表達來抑制肝癌的發(fā)展。因此,基于let-7f機制的研究可以為肝癌治療提供潛在的靶點。
[Abstract]:Liver cancer is one of the most common malignant tumors in the world. It is usually found at a late stage with limited effects of conventional treatments such as resection, liver transplantation, and so on, leading to a lack of effective treatment for this disease.Poor prognosis. MicroRNA is a short chain noncoding RNAs that perform posttranscriptional regulation by targeting silencing target genes.More and more evidence suggests that microRNA plays an important role in liver development, regeneration and metabolism.Since microRNA plays an important role in tumorigenesis and progression based on pathological response, it is necessary to clarify the pathological mechanism of microRNA imbalance for the diagnosis and treatment of the disease.We transfected mimics and inhibitor of let-7f in hepatoma cell line, and the results showed that let-7f was a tumor suppressor gene.Then the bioinformatics algorithm RNA22 was used to predict that the target of let-7f was c-Met and the target was detected by luciferase reporter gene and verified by Western blotting.We found that c-Met is a target of let-7f and plays a promoting role in the proliferation and metastasis of HCC.In vitro, let-7f could inhibit the proliferation and metastasis of hepatoma cells, which could be partly reversed by the restoration of c-Met expression.We are now conducting further bioinformatics analysis to identify let-7f and c-Met related signaling pathways and to further elucidate in vivo the role of low expression of let-7f in the pathogenesis and development of liver cancer.In general, we demonstrated in vitro that let-7f inhibits the development of liver cancer by targeting the expression of c-Met.Therefore, the research based on let-7f mechanism can provide potential targets for liver cancer therapy.
【學位授予單位】：中國科學技術(shù)大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R735.7

【參考文獻】

相關(guān)期刊論文 前1條

1 Tom Treasure;Miel Miloevi;Francesca Fiorentino;Joachim Pfannschmidt;;History and present status of pulmonary metastasectomy in colorectal cancer[J];World Journal of Gastroenterology;2014年40期

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本文編號：1744430