既往研究认为程序性死亡配体1（PD-L1）通过抑制免疫功能影响肿瘤预后，但肿瘤细胞内部PD-L1表达对细胞增殖是否有直接调节作用尚不完全清楚。我们原创性研究证实BRAF突变肠癌细胞中PD-L1高表达，敲减PD-L1可抑制细胞增殖；筛选发现PD-L1能够与THRAP3在细胞核内结合，并解除THRAP3对BUB1的抑制而加速细胞周期进程；BRAF V600E突变可上调转录因子LEF-1继而促进PD-L1转录。本研究将利用GST-Pulldown、ChIP等方法揭示PD-L1与THRAP3直接结合，LEF-1引起PD-L1表达上调机制；旨在进一步阐明肠癌细胞BRAF V600E突变通过高表达的LEF-1上调PD-L1，PD-L1在细胞核内与THRAP3结合上调BUB1促进肠癌细胞增殖。研究结果将为认识PD-L1除免疫抑制外，还在细胞核内对BRAF突变肠癌增殖发挥独特的调节作用提供依据。

Previous studies have shown that Programmed death ligand 1 (PD-L1) affects tumor prognosis by inhibiting immune function, but whether the expression of PD-L1 within tumor cells directly regulates cell proliferation is not fully understood. Our original study confirmed that PD-L1 was upregulated in BRAF mutant colorectal cancer cells, also interfering with PD-L1 can inhibit the proliferation of colorectal cancer. Screening showed that PD-L1 bound THRAP3 in the nucleus that release the inhibition of BUB1 by THRAP3 thereby promoting cell cycle progression. The BRAF V600E mutation promote the transcription of PD-L1 in colorectal cancer by upregulating LEF-1. This study will use GST-pulldown to prove the direct combination of PD-L1 and THRAP3. ChIP and other methods will be implemented to reveal the mechanism of PD-L1 upregulation caused by LEF-1. This project intends to elucidate that BRAF V600E mutation promotes the expression of PD-L1 in colorectal cancer by upregulating the transcription factor LEF-1, which binds to THRAP3 to upregulate BUB1 in the nucleus to promote the proliferation of colorectal cancer cells. The results will provide a basis for understanding that PD-L1 plays a unique regulatory role in the proliferation of BRAF mutant colorectal cancer in the nucleus besides immunosuppression.