Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
Bio-Bank of Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
Cancer Med. 2024 Jul;13(13):e7424. doi: 10.1002/cam4.7424.
Gastric cancer (GC) is the fourth leading cause of cancer-related death worldwide. Minichromsome maintenance proteins family member 8 (MCM8) assists DNA repair and DNA replication. MCM8 exerts tumor promotor function in multiple digestive system tumors. MCM8 is also considered as a potential cancer therapeutic target.
Bioinformatics methods were used to analyze MCM8 expression and clinicopathological significance. MCM8 expression was detected by immunohistochemistry (IHC) staining and qRT-PCR. MCM8 functions in GC cell were explored by Celigo cell counting, colony formation, wound-healing, transwell, and annexin V-APC staining assays. The target of MCM8 was determined by human gene expression profile microarray. Human phospho-kinase array kit evaluated changes in key proteins after ribosomal protein S15A (RPS15A) knockdown. MCM8 functions were reassessed in xenograft mouse model. IHC detected related proteins expression in mouse tumor sections.
MCM8 was significantly upregulated and predicted poor prognosis in GC. High expression of MCM8 was positively correlated with lymph node positive (p < 0.001), grade (p < 0.05), AJCC Stage (p < 0.001), pathologic T (p < 0.01), and pathologic N (p < 0.001). MCM8 knockdown inhibited proliferation, migration, and invasion while promoting apoptosis. RPS15A expression decreased significantly after MCM8 knockdown. It was also the only candidate target, which ranked among the top 10 downregulated differentially expressed genes (DEGs) in sh-MCM8 group. RPS15A was identified as the target of MCM8 in GC. MCM8/RPS15A promoted phosphorylation of P38α, LYN, and p70S6K. Moreover, MCM8 knockdown inhibited tumor growth, RPS15A expression, and phosphorylation of P38α, LYN, and p70S6K in vivo.
MCM8 is an oncogene and predicts poor prognosis in GC. MCM8/RPS15A facilitates GC progression.
胃癌（GC）是全球导致癌症死亡的第四大原因。微小染色体维持蛋白家族成员 8（MCM8）有助于 DNA 修复和 DNA 复制。MCM8 在多种消化系统肿瘤中发挥肿瘤促进因子的作用。MCM8 也被认为是一种有潜力的癌症治疗靶点。
使用生物信息学方法分析 MCM8 的表达和临床病理意义。通过免疫组织化学（IHC）染色和 qRT-PCR 检测 MCM8 的表达。通过 Celigo 细胞计数、集落形成、划痕愈合、Transwell 和 Annexin V-APC 染色实验探索 MCM8 在 GC 细胞中的功能。通过人类基因表达谱微阵列确定 MCM8 的靶标。人类磷酸激酶阵列试剂盒评估核糖体蛋白 S15A（RPS15A）敲低后关键蛋白的变化。在异种移植小鼠模型中重新评估 MCM8 的功能。IHC 检测小鼠肿瘤组织中相关蛋白的表达。
MCM8 在 GC 中显著上调并预测预后不良。MCM8 高表达与淋巴结阳性（p<0.001）、分级（p<0.05）、AJCC 分期（p<0.001）、病理 T（p<0.01）和病理 N（p<0.001）呈正相关。MCM8 敲低抑制增殖、迁移和侵袭，同时促进凋亡。MCM8 敲低后 RPS15A 表达显著下降。它也是唯一的候选靶点，在 sh-MCM8 组中排名前 10 位下调的差异表达基因（DEGs）之一。RPS15A 被鉴定为 GC 中 MCM8 的靶点。MCM8/RPS15A 促进了 P38α、LYN 和 p70S6K 的磷酸化。此外，MCM8 敲低抑制了肿瘤生长、RPS15A 表达以及体内 P38α、LYN 和 p70S6K 的磷酸化。
MCM8 是一种癌基因，可预测 GC 的预后不良。MCM8/RPS15A 促进 GC 进展。
