融合基因
ETV6
融合蛋白
生物
增强子
癌症研究
转录因子
基因
分子生物学
遗传学
染色体易位
重组DNA
作者
Angana Biswas,Y. Rajesh,Subhayan Das,Indranil Banerjee,Neelkamal Kapoor,Pralay Mitra,Mahitosh Mandal
出处
期刊:Cancer Letters
[Elsevier]
日期:2022-09-01
卷期号:544: 215811-215811
被引量:3
标识
DOI:10.1016/j.canlet.2022.215811
摘要
Fusion genes are abnormal genes resulting from chromosomal translocation, insertion, deletion, inversion, etc. ETV6, a rather promiscuous partner forms fusions with several other genes, most commonly, the NTRK3 gene. This fusion leads to the formation of a constitutively activated tyrosine kinase which activates the Ras-Raf-MEK and PI3K/AKT/MAPK pathways, leading the cells through cycles of uncontrolled division and ultimately resulting in cancer. Targeted therapies against this ETV6-NTRK3 fusion protein are much needed. Therefore, to find a targeted approach, a transcription factor RBPJ regulating the ETV6 gene was established and since the ETV6-NTRK3 fusion gene is downstream of the ETV6 promoter/enhancer, this fusion protein is also regulated. The regulation of the ETV6 gene via RBPJ was validated by ChIP analysis in human glioblastoma (GBM) cell lines and patient tissue samples. This study was further followed by the identification of an inhibitor, Furamidine, against transcription factor RBPJ. It was found to be binding with the DNA binding domain of RBPJ with antitumorigenic properties and minimal organ toxicity. Hence, a new target RBPJ, regulating the production of ETV6 and ETV6-NTRK3 fusion protein was found along with a potent RBPJ inhibitor Furamidine.
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