Clinical appliciation of cancer treatment by revealing alternative splicing mechanism of c-myc transcriptional suppressor FBP-interacting repressor

最近，FBP相互作用的抑制因子FIR和TFIIH/p89/XPB解旋酶之间的相互作用被发现能够抑制c-myc的转录，因此可能在抑制肿瘤形成中起重要作用。此外，FIR的强制表达可诱导细胞凋亡。FIR氨基末端抑制域的缺失和c-Myc与FIR共表达可使细胞免于凋亡。因此，c-myc的抑制介导了FIR诱导的细胞凋亡。一种FIR的剪接变异体既不能抑制c-myc，也不能促进细胞凋亡，在人类原发结直肠癌中经常被发现，但在邻近的正常组织中却没有。本研究对腺病毒或仙台病毒FIR表达载体的抗肿瘤效果进行了检测。此外，在结直肠癌患者外周血中还检测到FIR剪接变异体的蛋白或mRNA水平。

Recently, an interaction between FBP-interacting repressor, FIR, and TFIIH/p89/XPB helicase was found to repress c-myc transcription and so might be important for sippressing tumor formation. Further, enforced expression of FIR induced apoptosis. Deletion of FIR's amino terminal repression domain rescued thecells from apoptosis, as did co-expression of c-Myc with FIR. Thus repression of c-myc mediates FIR-driven apoptosis. A splicing variant of FIR unable to repress c-myc nor driving apoptosis was frequently discovered in human primary colorectal cancers, but not in the adjacent normal tissues. In this study, adeno- or Sendai virus FIR expression vector was examined its anti-tumor efficacy. Additionally, FIR splicing variant was detected at their protein or mRNA level in the peripheral blood of colorectal cancer patients.