低表达let-7f在肝癌增殖和转移过程中功能机制研究

发布时间：2018-04-13 12:10

本文选题：肝癌 + microRNA　；参考：《中国科学技术大学》2016年硕士论文

【摘要】：肝癌是世界上最常见的恶性肿瘤之一,一般发现的时候都是晚期且常规治疗手段如切除、移植肝脏等效果十分有限,导致这种疾病没有很好的治疗疗效,预后差。microRNA是一种短链非编码RNA,通过靶向沉默靶基因行使转录后调控功能。越来越多的证据表明microRNA在肝脏的发育、再生、代谢过程中发挥着重要的调控作用。由于microRNA在肿瘤发生发展中基于病理反应会发生微调作用,所以阐明microRNA失调造成的病理机制对于疾病的诊断和治疗都非常有必要。我们在肝癌细胞系中分别转染let-7f的mimics和抑制物,实验结果反应let-7f是一个抑癌基因。随后使用生物信息学算法RNA22预测了let-7f的靶点为c-Met并且通过荧光素酶报告基因检测及免疫印迹验证。我们发现c-Met是let-7f的靶点,并且在肝癌的增殖转移过程中起到促进作用。通过体外实验,let-7f可以抑制肝癌细胞的增殖与转移,这种作用可以部分地因恢复c-Met表达而逆转。我们现在正在进行更深入的生物信息学分析,找到let-7f以及c-Met相关信号通路并且准备在体内实验中更深入地阐明let-7f低表达在肝癌发生发展中的作用。总的来说,我们通过体外实验阐明了let-7f通过靶向抑制c-Met的表达来抑制肝癌的发展。因此,基于let-7f机制的研究可以为肝癌治疗提供潜在的靶点。
[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.
【学位授予单位】：中国科学技术大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R735.7

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