AUTHOR=Zhang Su-Yun , Luo Qiong , Xiao Li-Rong , Yang Fan , Zhu Jian , Chen Xiang-Qi , Yang Sheng 

TITLE=Role and mechanism of NCAPD3 in promoting malignant behaviors in gastric cancer

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1341039

DOI=10.3389/fphar.2024.1341039

ISSN=1663-9812

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