HBV上调的hsa_circ_0007807竞争性结合miR-1249-5p调控TPX2在肝癌发生发展中的作用及机制研究
批准号:
82060446
项目类别:
地区科学基金项目
资助金额:
34.0 万元
负责人:
晏少颖
依托单位:
学科分类:
肿瘤细胞命运
结题年份:
2024
批准年份:
2020
项目状态:
已结题
项目参与者:
晏少颖
中文摘要
环状RNA(circRNA)在肿瘤发生发展中有重要的调控作用,但其在HBV相关肝癌中的作用尚不清楚。我们前期通过测序技术及qRT-PCR发现circ_0007807在HBV阳性肝癌细胞及组织中高表达,并可促进肝癌细胞增殖和转移能力;HBV可通过HBx诱导circ_0007807表达;circ_0007807与miR-1249-5p存在序列互补并相互负调控其表达,TPX2与miR-1249-5p也存在结合位点,且与miR-1249-5p负相关,与circ_0007807正相关。据此推测:HBV上调的circ_0007807通过竞争性结合miR-1249-5p上调TPX2的表达进而促进肝癌增殖和转移。本研究拟从细胞、病人组织及动物水平等多层次阐明circ_0007807/miR-1249-5p/TPX2轴作用于肝癌的分子机制,以期为HBV相关肝癌提供circRNA导向的诊断及治疗靶标。
英文摘要
CircRNA plays an important role in the occurrence and development of tumors, but its role in HBV related liver cancer is not clear. We found that circ_0007807 was highly expressed in HBV positive HCC cells and tissues by sequencing technology and qRT-PCR, and it could promote the proliferation and metastasis of HCC cells; While HBV could enhance its transcription through HBx; circ_0007807 and miR-1249-5p could not only complement each other in sequence, but also negatively regulate each other's expression, TPX2 and miR-1249-5p also have binding sites, and TPX2 was negatively correlated with miR-1249-5p and positively correlated with circ_0007807. It can be concluded that HBV-upregulated circ_0007807 competitive binding miR-1249-5p to upregulate the expression of TPX2, thus promoting the proliferation and metastasis of HCC cells. This study will further clarify the molecular mechanism of circ_0007807/miR-1249-5p/TPX2 axis acting on HCC cells, using cell, patient tissue and animal model, so as to provide a circRNA-oriented target for diagnosis and treatment of HBV related HCC.
乙型肝炎病毒(HBV)感染是肝癌发生的主要诱因,但是其具体机制仍不明确。环状RNA(circRNA)在癌症发生发展中有着重要的调控作用,但其作用机制有待进一步探究。本研究发现HBV通过编码的乙型肝炎病毒蛋白X(HBx)增强hsa_circ_0007807的转录而上调其表达,而hsa_circ_0007807在HBV相关肝癌细胞及组织中上调,并可通过作为miRNA天然的诱饵,竞争性结合miR-1249-5p,在转录后调控水平充当ceRNA上调其下游靶基因TPX2的表达,进而促进肝癌细胞的增殖和转移。该研究为HBV相关肝癌发生发展的分子机制研究提供新的思路,并为HBV相关肝癌提供circRNA导向的诊断和治疗的新方法。
国内基金
海外基金