Department of Chemotherapy, Affiliated Hospital of Nantong University, Nantong, China.
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China.
Oxid Med Cell Longev. 2022 Feb 16;2022:2946989. doi: 10.1155/2022/2946989. eCollection 2022.
Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide nowadays. Block of proliferation 1 (BOP1), a nucleolar protein involved in rRNA processing and ribosome assembly, is associated with tumor development in certain cancers of digestive system. Therefore, we hypothesized that BOP1 might play an important role in gastric cancer development.
Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) were used to identify the differentially expressed genes and their clinical relevance. qPCR and western blot were performed further to examine the levels of BOP1 mRNA and protein, respectively. Cell viability, apoptosis, migration and invasion were investigated in gastric cancer cell lines with BOP1 silencing or overexpression. The epithelial mesenchymal transition (EMT) associated proteins, including E-cadherin and N-cadherin, were measured using immunoblotting. Finally, the downstream pathway of BOP1 were explored using bioinformatic analysis and qPCR.
BOP1 was found up-regulated in gastric tumor tissues compared with paired normal tissues (P < 0.0001). Its expression was associated with more advanced pathological grades (P = 0.0006) and tumor location (P = 0.002), as well as a poor survival (HR 1.27, P = 0.015). BOP1 expression was increased in 4 kind of tumor cell lines compared with the normal group. The overexpression of BOP1 promoted cell proliferation and inhibit cell apoptosis, while silencing BOP1 showed a reversed trend. Immunoblotting results suggested that BOP enhanced N-cadherin, a mesenchymal marker, while reduced E-cadherin, an epithelial marker. Finally, bioinformatic prediction showed that the cell cycle could be a downstream pathway of BOP1.
The present study demonstrated that BOP1 contributed to the development of gastric cancer by promoting proliferation, invasion and epithelial mesenchymal transformation, which could be a biomarker or therapeutic target in GC.
胃癌（GC）是当今全球癌症相关死亡的主要原因之一。增殖 1 阻断蛋白（BOP1）是一种参与 rRNA 加工和核糖体组装的核仁蛋白，与某些消化系统癌症的肿瘤发展有关。因此，我们假设 BOP1 可能在胃癌的发展中发挥重要作用。
使用基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）来鉴定差异表达的基因及其临床相关性。进一步进行 qPCR 和 Western blot 以分别检测 BOP1 mRNA 和蛋白的水平。使用 BOP1 沉默或过表达的胃癌细胞系研究细胞活力、凋亡、迁移和侵袭。使用免疫印迹法测量上皮-间充质转化（EMT）相关蛋白，包括 E-钙粘蛋白和 N-钙粘蛋白。最后，使用生物信息学分析和 qPCR 探索 BOP1 的下游通路。
与配对的正常组织相比，在胃癌肿瘤组织中发现 BOP1 上调（P<0.0001）。其表达与更晚期的病理分级（P=0.0006）和肿瘤位置（P=0.002）相关，并且生存不良（HR 1.27，P=0.015）。与正常组相比，在 4 种肿瘤细胞系中 BOP1 的表达增加。BOP1 的过表达促进细胞增殖并抑制细胞凋亡，而沉默 BOP1 则表现出相反的趋势。免疫印迹结果表明，BOP 增强了间充质标志物 N-钙粘蛋白，同时降低了上皮标志物 E-钙粘蛋白。最后，生物信息学预测表明细胞周期可能是 BOP1 的下游通路。
本研究表明，BOP1 通过促进增殖、侵袭和上皮-间充质转化促进胃癌的发展，可能成为 GC 的生物标志物或治疗靶点。
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