外泌体circPTK2调控miR-129-5p/BMP-2信号轴在肝癌进展中的作用及分子机制

肝细胞癌(HCC)的高复发和强侵袭转移能力是影响预后的关键因素，其分子机制尚不清楚。环状RNA（circRNA）异常表达与肿瘤的发生发展密切相关。我们前期研究发现:（1）高转移潜能肝癌细胞源性外泌体中circPTK2表达水平上调，并且能够促进肝癌细胞的侵袭和转移；（2）生物信息学分析提示肝癌源性外泌体circPTK2能够靶向miR-129-5p/BMP-2信号轴；（3）上调BMP-2表达可明显促进肝癌细胞的增殖和侵袭。我们由此推测circPTK2可能通过调控miR-129-5p/BMP-2信号轴来影响肝癌的进展及转移。本研究拟利用肝癌细胞系、异种移植瘤模型和临床肝癌样本，从动物、细胞、分子等多层面探究外泌体介导的circPKT2对肝癌增殖和侵袭的调控作用，并进一步阐释circPTK2调控miR-129-5p/BMP-2信号轴影响肝癌发展的分子机制，为筛选新的肝癌治疗靶点提供理论依据。

The high recurrence and strong invasion and metastasis of hepatocellular carcinoma（HCC）are the key factors influencing the prognosis. However, the underlying molecular mechanisms remain elusive. Abnormal expression of circRNA is closely related to the occurrence and development of tumors.Our previous studies showed that the up-regulated circPTK2 derived from exosomes in the highly metastatic HCCs promoted the invasion and migration of HCC cells. Bioinformatics analysis revealed that HCC exosomes-derived circPTK2 can target the miR-129-5p/BMP-2 axis.Up-regulation of bmp-2 expression can significantly promote the proliferation and invasion of HCC cells .We speculate that circPTK2 may affect the progression and metastasis of HCC by regulating the miR-129-5p/BMP-2 signaling pathway. This study intends to use hepatocellular carcinoma cell lines, xenograft tumor models and clinical HCC samples to explore and clarify the regulatory effects of exosome-derived circPKT2 on HCC proliferation, invasion and migration both in vitro and in vivo. This study may underscore the importance of circPTK2/miR-129-5p/BMP-2 signaling pathway in regulating the progression and metastasis of HCC.