Lei Chun, Hou Yafeng, Chen Jiong
Department of General Surgery, Tongling People's Hospital, Tongling, Anhui 244009, P.R. China.
Department of General Surgery, Tongling People's Hospital Affiliated to Wannan Medical College, Tongling, Anhui 244009, P.R. China.
Exp Ther Med. 2021 Dec;22(6):1459. doi: 10.3892/etm.2021.10894. Epub 2021 Oct 20.
Bone marrow stromal cell antigen 2 (BST2) has been reported to act as an oncogene in the tumorigenesis of numerous types of cancer. Bioinformatics analysis has predicted the binding interaction between BST2 and specificity protein 1 (SP1) and the involvement of SP1 in pancreatic cancer. Therefore, the present study set out to verify this interaction and determine how it may affect pancreatic cancer progression. Normal human pancreatic duct epithelial cells (HPDE6-C7) and pancreatic cancer cell lines (SW1990, BxPC3, PANC1 and PSN-1) were selected for western blotting and reverse transcription-quantitative PCR detection of BST2 expression. Colony formation, Cell Counting Kit-8 and wound healing assays were performed to detect the proliferative and migratory abilities of PANC1 cells following transfection with small interfering RNA against BST2. The expression of proliferation and migration markers were assayed using western blotting. Chromatin immunoprecipitation and luciferase reporter assays were employed to verify the bioinformatics prediction of BST2-SP1 binding. PANC1 cell proliferation and migration were analyzed following BST2 knockdown and SP1 overexpression. In comparison with HPDE6-C7 cells, all four pancreatic cancer cell lines were found to exhibit increased BST2 expression levels to varying degrees, with the highest levels observed in PANC1 cells. BST2 knockdown inhibited PANC1 cell colony formation, proliferation and migration. Additionally, SP1 was shown to bind to the BST2 promoter and could promote PANC1 cell proliferation and migration when overexpressed. However, BST2 knockdown rescued SP1 overexpression-induced PANC1 cell colony formation, proliferation and migration. In conclusion, activation of BST2 by the transcription factor SP1 was shown to accelerate pancreatic cancer cell proliferation and migration, suggesting that BST2 and SP1 may be plausible therapeutic targets in targeted therapy for pancreatic cancer.
据报道，骨髓基质细胞抗原2（BST2）在多种癌症的肿瘤发生过程中作为一种癌基因发挥作用。生物信息学分析预测了BST2与特异性蛋白1（SP1）之间的结合相互作用以及SP1在胰腺癌中的参与情况。因此，本研究着手验证这种相互作用，并确定其如何影响胰腺癌的进展。选择正常人胰腺导管上皮细胞（HPDE6-C7）和胰腺癌细胞系（SW1990、BxPC3、PANC1和PSN-1）进行BST2表达的蛋白质印迹法和逆转录定量PCR检测。进行集落形成、细胞计数试剂盒-8和伤口愈合试验，以检测用针对BST2的小干扰RNA转染后PANC1细胞的增殖和迁移能力。使用蛋白质印迹法检测增殖和迁移标志物的表达。采用染色质免疫沉淀和荧光素酶报告基因试验来验证BST2-SP1结合的生物信息学预测。在BST2敲低和SP1过表达后分析PANC1细胞的增殖和迁移。与HPDE6-C7细胞相比，发现所有四种胰腺癌细胞系均不同程度地表现出BST2表达水平升高，其中在PANC1细胞中观察到的水平最高。BST2敲低抑制了PANC1细胞的集落形成、增殖和迁移。此外，SP1被证明与BST2启动子结合，并且在过表达时可促进PANC1细胞的增殖和迁移。然而，BST2敲低挽救了SP1过表达诱导的PANC1细胞集落形成、增殖和迁移。总之，转录因子SP1对BST2的激活被证明可加速胰腺癌细胞的增殖和迁移，这表明BST2和SP1可能是胰腺癌靶向治疗中合理的治疗靶点。
