Ma Ning, Zhao Sihui, Yang Wei, Wang Yongfang
Department of General Surgery Ⅱ, the First People's Hospital of Yunnan Province, the Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, Yunnan Province, China.
Department of General Surgery Ⅱ, the First People's Hospital of Yunnan Province, the Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, Yunnan Province, China.
Arab J Gastroenterol. 2023 Aug;24(3):168-174. doi: 10.1016/j.ajg.2023.02.004. Epub 2023 Mar 4.
The B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) is associated with the progression of gastric cancer (GC). However, its role in drug resistance of gastric cancer stem cell (GCSC) remains unclear. This study aimed to explore the biological function of BMI-1 in GC cells and its role in drug resistance of GCSCs.
We assessed BMI-1 expression in the GEPIA database and in our collected samples from patients with GC. We silenced BMI-1 using siRNA to study the cell proliferation and migration of GC cells. We also used Hoechst 33342 staining to verify the effect of adriamycin (ADR) on side population (SP) cells, and measured the effects of BMI-1 on the expression of N-cadherin, E-cadherin, and drug-resistance-related proteins (multidrug resistance mutation 1 and lung resistance-related protein). Finally, we analyzed BMI-1-related proteins uing the STRING and GEPIA databases.
BMI-1 mRNA was upregulated in GC tissues and cell lines, especially in MKN-45 and HGC-27 cells. Silencing BMI-1 reduced the proliferation and migration of GC cells. Knocking down BMI-1 significantly decreased epithelial-mesenchymal transition progression, expression levels of drug-resistant proteins, and the number of SP cells in ADR-treated GC cells. Bioinformatics analysis showed that EZH2, CBX8, CBX4, and SUZ12 were positively correlated with BMI-1 in GC tissues.
Our study demonstrates that BMI-1 affects the cellular activity, proliferation, migration, and invasion of GC cells. Silencing the BMI-1 gene significantly reduces the number of SP cells and the expression of drug-resistant proteins in ADR-treated GC cells. We speculate that inhibition of BMI-1 increases the drug resistance of GC cells by affecting GCSCs, and that EZH2, CBX8, CBX4, and SUZ12 may participate in BMI-1-induced enhancement of GCSC-like phenotype and viability.
B细胞特异性莫洛尼鼠白血病病毒整合位点1（BMI-1）与胃癌（GC）的进展相关。然而，其在胃癌干细胞（GCSC）耐药中的作用仍不清楚。本研究旨在探讨BMI-1在GC细胞中的生物学功能及其在GCSC耐药中的作用。
我们在GEPIA数据库以及我们收集的GC患者样本中评估BMI-1的表达。我们使用小干扰RNA（siRNA）沉默BMI-1以研究GC细胞的增殖和迁移。我们还使用Hoechst 33342染色来验证阿霉素（ADR）对侧群（SP）细胞的影响，并测量BMI-1对N-钙黏蛋白、E-钙黏蛋白和耐药相关蛋白（多药耐药突变1和肺耐药相关蛋白）表达的影响。最后，我们使用STRING和GEPIA数据库分析与BMI-1相关的蛋白。
BMI-1 mRNA在GC组织和细胞系中上调，尤其是在MKN-45和HGC-27细胞中。沉默BMI-1可降低GC细胞的增殖和迁移。敲低BMI-1显著降低上皮-间质转化进程、耐药蛋白的表达水平以及ADR处理的GC细胞中SP细胞的数量。生物信息学分析表明，在GC组织中，EZH2、CBX8、CBX4和SUZ12与BMI-1呈正相关。
我们的研究表明，BMI-1影响GC细胞的细胞活性、增殖、迁移和侵袭。沉默BMI-1基因可显著减少ADR处理的GC细胞中SP细胞的数量和耐药蛋白的表达。我们推测，抑制BMI-1通过影响GCSC增加GC细胞的耐药性，并且EZH2、CBX8、CBX4和SUZ12可能参与BMI-1诱导的GCSC样表型和活力增强。
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