基于融合基因BMS1P20-LOC102724580环化的F-circRNA-B/L调控脑胶质瘤恶性演进的鉴定与机制研究

Both chromosomal aberration and non-coding RNA are crucial for glioblastoma genesis and progression，but how does the chromosomal aberration effect the non-coding RNA is barely unknown. The proposer has found the repetitive chromosomal aberration event could produce a new fusion gene: BMS1P20-LOC102724580, and this fusion gene could generate a new circRNA: f-circRNA-B/L. The results showed that the glioma U87 cells could enhanced migration and proliferation ability, after transferred the f-circRNA-B/L, moreover, the Akt pathway was also activated. On this basis, the proposer plan to use cell transfection, chromatin immunoprecipitation assay, qPCR, WB et al to further explore and identify the ceRNA mechanism in glioblastoma..This research may provide insides for understanding the comprehensive bio-mechanism of glioblastoma, the fusion gene, BMS1P20-LOC102724580 , is expected to be new target therapy method, the f-circRNA-B/L is expected to be new liquid biopsy criterion for glioblastoma, which contains the potential clinical transfer value.

染色体畸变和非编码RNA调控均在胶质母细胞瘤的恶性演进中起重要作用，而胶质母细胞瘤中染色体畸变对于非编码RNA的影响尚不明确。申请人前期发现重复性的染色体畸变事件可以产生新型融合基因BMS1P20-LOC102724580，且基于该融合基因可以环化新型的环状RNA：f-circRNA-B/L。前期结果显示，过表达f-circRNA-B/L后，胶质瘤U87细胞侵袭性和增殖能力增强，Akt信号通路活化。在此基础上，申请人提出科学假设：部分胶质瘤中存在BMS1P20-LOC102724580 - f-circRNA-B/L - AKT pathway调控模式。拟通过细胞转染、免疫沉淀，qPCR，WB，生物信息学等技术进一步探索和验证f-circRNA-B/L影响胶质母细胞瘤的ceRNA调控机制。本研究有望为胶质母细胞瘤恶性演进补充新的致病机制和提供治疗靶点，并具有临床转化价值。

染色体畸变和非编码RNA调控均在胶质母细胞瘤的恶性演进中起重要作用，而胶质母细胞瘤中染色体畸变对于非编码RNA的影响尚不明确。申请人在本课题中发现重复性的染色体畸变事件可以产生新型融合基因BMS1P20-LOC102724580，且基于该融合基因可以环化新型的环状RNA：f-circRNA-B/L。前期结果显示，过表达f-circRNA-B/L后，胶质瘤U87细胞侵袭性和增殖能力增强，Akt信号通路活化。在此基础上，申请人验证了之前提出的科学假设：部分胶质瘤中存在BMS1P20-LOC102724580 - f-circRNA-B/L - AKT pathway调控模式。进一步通过细胞转染、免疫沉淀，qPCR，WB，生物信息学等技术进一步探索和验证f-circRNA-B/L影响胶质母细胞瘤的ceRNA调控机制，发现了过表达 f-circRNA-B/L后对胶质瘤细胞恶性生物学行为的改变。本研究有望为胶质母细胞瘤恶性演进补充新的致病机制和提供治疗靶点，并具有一定的临床转化价值。.在本自然科学基金的支持下，申请人顺利完成科学假设的验证，并发表相关论文7篇。