DataSheet13_Role and mechanism of NCAPD3 in promoting malignant behaviors in gastric cancer.xlsx

Background:Gastric cancer (GC) is one of the major malignancies threatening human lives and health. Non-SMC condensin II complex subunit D3 (NCAPD3) plays a crucial role in the occurrence of many diseases. However, its role in GC remains unexplored.Materials and Methods:The Cancer Genome Atlas (TCGA) database, clinical samples, and cell lines were used to analyze NCAPD3 expression in GC. NCAPD3 was overexpressed and inhibited by lentiviral vectors and the CRISPR/Cas9 system, respectively. The biological functions of NCAPD3 were investigated in vitro and in vivo. Gene microarray, Gene set enrichment analysis (GSEA) and ingenuity pathway analysis (IPA) were performed to establish the potential mechanisms.Results:NCAPD3 was highly expressed in GC and was associated with a poor prognosis. NCAPD3 upregulation significantly promoted the malignant biological behaviors of gastric cancer cell, while NCAPD3 inhibition exerted a opposite effect. NCAPD3 loss can directly inhibit CCND1 and ESR1 expression to downregulate the expression of downstream targets CDK6 and IRS1 and inhibit the proliferation of gastric cancer cells. Moreover, NCAPD3 loss activates IRF7 and DDIT3 to regulate apoptosis in gastric cancer cells.Conclusion:Our study revealed that NCAPD3 silencing attenuates malignant phenotypes of GC and that it is a potential target for GC treatment.

背景：胃癌（GC）是人类生命与健康面临的主要恶性肿瘤之一。非SMC凝聚素II复合物亚基D3（NCAPD3）在多种疾病的发病机制中扮演着至关重要的角色。然而，其在胃癌中的功能尚未得到充分研究。材料与方法：本研究利用癌症基因组图谱（TCGA）数据库、临床样本和细胞系，分析了胃癌中NCAPD3的表达情况。通过慢病毒载体过表达NCAPD3，并通过CRISPR/Cas9系统抑制其表达。在体外和体内实验中，探讨了NCAPD3的生物功能。通过基因微阵列、基因集富集分析（GSEA）和通路分析（IPA）来确立潜在的分子机制。结果：在胃癌中，NCAPD3的表达水平显著升高，且与不良预后相关。NCAPD3的上调显著促进了胃癌细胞的恶性生物学行为，而其抑制则产生了相反的效果。NCAPD3的缺失可以直接抑制CCND1和ESR1的表达，从而下调下游靶标CDK6和IRS1的表达，并抑制胃癌细胞的增殖。此外，NCAPD3的缺失还可以激活IRF7和DDIT3，调节胃癌细胞的凋亡。结论：本研究揭示了NCAPD3的沉默可以减轻胃癌的恶性表型，并且NCAPD3是胃癌治疗的潜在靶点。