The CCDC43-ADRM1 axis regulated by YY1, promotes proliferation and metastasis of gastric cancer.
Previous studies have shown an association between coiled-coil domain-containing (CCDC) genes and different cancers. Our previous studies revealed that CCDC43 is highly expressed in colorectal cancer, but the expression and molecular mechanisms of CCDC43 in gastric cancer (GC) are yet to be determined. Here, we show that CCDC43 is overexpressed in gastric tissues. CCDC43 expression is closely related to tumor differentiation, lymph-node-metastasis, and prognosis of gastric cancer. Overexpression of CCDC43 promotes the proliferation, invasion, and metastasis of GC cells. CCDC43 may upregulate and stabilize ADRM1, resulting in the construction of the ubiquitin-mediated proteasome. In contrast, inhibition of ADRM1 could reverse the function of CCDC43 in GC both in vitro and in vivo. Our data demonstrate that transcription factor YY1 directly binds to CCDC43 and ADRM1 gene promoters, leading to over-expression of CCDC43 and ADRM1. Furthermore, in vitro experiments demonstrate that knock down of CCDC43 or ADRM1 attenuates the YY1-mediated malignant phenotypes. Finally, the association among YY1, CCDC43 and ADRM1 is validated in clinical samples. Our findings suggest that the CCDC43-ADRM1 axis regulated by YY1, promotes proliferation and metastasis of GC, and the axis may be a potential therapeutic target for GC.
['Wang|Jing|J|', 'Wu|Xiaosheng|X|', 'Dai|Weiyu|W|', 'Li|Jiaying|J|', 'Xiang|Li|L|', 'Tang|Weimei|W|', 'Lin|Jianjiao|J|', 'Zhang|Wenjing|W|', 'Liu|Guangnan|G|', 'Yang|Qiong|Q|', 'Lin|Zhizhao|Z|', 'Sun|Yong|Y|', 'Zhang|Yi|Y|', 'Chen|Yaying|Y|', 'Li|Guoxin|G|', 'Li|Aimin|A|', 'Liu|Side|S|', 'Li|Yue|Y|', 'Wang|Jide|J|']
D000818:Animals D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D015972:Gene Expression Regulation, Neoplastic D006801:Humans D047908:Intracellular Signaling Peptides and Proteins D008175:Lung Neoplasms D051379:Mice D009363:Neoplasm Proteins D009368:Neoplasm Transplantation D011379:Prognosis D013274:Stomach Neoplasms D016019:Survival Analysis D015854:Up-Regulation D050986:YY1 Transcription Factor
YY1 Metastasis Gastric cancer CCDC43 ADRM1