环状RNA在肝癌血管拟态形成中的实验初探

Hepatocellular carcinoma (HCC) is one of the most common malignant tumours in China. Although recently the diagnosis and the therapy of HCC has made a big progress, the morbidity and mortality didn’t improve notably. HCC is a hypervascular solid tumor that primarily exhibits aberrant angiogenesis. Previous studies indicated that only endothelial cells could form blood vessels to support the growth of malignant tumors; however, recent studies have revealed several new patterns by which tumor tissues nourish themselves. As a new tumor blood supply mode, vasculogenic mimicry (VM) plays an important role in the early-stage metastasis of HCC. During the metastasis stages, the loss of epithelial (E)-cadherin expression and the subsequent loss of homotypic cellular adhesion may be a unique and important step that enables malignant epithelial cells to invade and metastasize normal cells. This mechanism characterizes a developmental regulatory program, the epithelial-to-mesenchymal transition (EMT). This process is regulated by various mechanisms. Non-coding RNA plays an important role in the process of EMT. As a new member of non-coding RNA, circular RNA has not been reported in VM. Circular RNA as the regulator of microRNA, is not only for the high expression level and stable structure, but also can downregulate the inhibition of microRNA of its target gene expression, as a result, the target gene could be upregulated. In this study, we plan to discover the relationship between citrcRNA and EMT & VM, and to explore the role of circular RNA in tumor invasion and metastasis. These results will not only enrich the theory of tumor angiogenesis, but also provide a new idea of treatment in clinical antitumor therapy.

肝细胞癌是我国最常见的恶性肿瘤之一，目前尚无有效治疗手段，与其丰富的血液供应密切相关。血管拟态作为肿瘤新的血液供应模式，在肝癌早期转移过程中起重要作用。上皮来源的肿瘤细胞通过自身塑形，获得间质表型，与宿主血管相连通，不仅营养自身，并延血道向远处转移。这一过程受多方面机制的调控。非编码RNA在上皮间质转变过程中发挥重要作用。环状RNA作为非编码RNA家族的新成员，尚未在血管拟态形成理论中报道。环状RNA作为微小RNA的环状抑制剂，不仅有表达水平高，结构稳定性好等优点，更能解除微小RNA对其靶基因的抑制作用，上调靶基因的表达水平。上皮钙粘蛋白的表达下调是肿瘤发生上皮间质转变的重要标志之一，以EMT和VM的表征蛋白作为靶基因探索相关环状RNA及微小RNA的作用机制，探究环状RNA在肿瘤侵袭转移中的作用，不仅丰富了肿瘤血管生成理论，更为临床抗肿瘤治疗提供新的治疗思路。