circ-SOX5在肝细胞癌恶性进展中的作用及机制

肝细胞癌(HCC)恶性度高，预后差，研究表明环状RNA在肿瘤进展发挥重要作用，但其在HCC的作用及机制均尚未清楚。我们前期发现环状RNA circ-SOX5 在HCC组织低表达，且与肿瘤恶性表型及预后差相关；预实验显示：(a) 沉默 circ-SOX5 后 miR-590-3p 表达增多并促进HCC增殖、迁移；(b) miR-590-3p抑制TRAF3表达；(c) 临床HCC样本中，TRAF3 与 SOX5 表达呈负相关。因此，我们提出circ-SOX5 通过 miR-590-3p 与 TRAF3 调控SOX5抑制HCC浸润转移的假说。本项目拟采用一系列免疫学及细胞生物学实验，明确 circ-SOX5在HCC中的表达与意义，阐述circ-SOX5/miR-590-3p/TRAF3/SOX5 通路在HCC细胞增殖、浸润转移中的作用及其机制，为诠释肝癌进展的分子机制和寻找靶向治疗提供科学依据。

Hepatocellular carcinoma (HCC) is one of the most prevalent manlignancies with high morbidity and mortality. However, the nature of HCC progression remains elusive. Previous studies suggest that circular RNA play an important role in human cancer progression. Previously, we found that circular RNA circ-SOX5 was down-regulated and significantly associated with malignant phenotype and poor prognosis of HCC. Our preliminary study showed that (a) knockdown circ-SOX5 markly increased the expression of miR-590-3p and promoted cell proliferation and migration; (b) miR-590-3p inhibited the expression of TRAF3; (c) TRAF3 expression was inversely correlated with the expresion of SOX5 in clinical HCC samples. Based on these findings, we assume that circ-SOX5 inhibits tumor invasion and metastasis via miR-590-3p and TRAF3 modulating SOX5. In this study, we aim to detemine the expression of circ-SOX5 and its clinical significance in HCC, to reveal the role and mechanism of circ-SOX5/miR-590-3p/TRAF3/SOX5 in cell proliferation, and invasion and metastasis in HCC. Our study is likely to provide not only solid evidence that circ-SOX5 is involved in HCC progression, but also a potential biomarker for HCC clinical management.