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.

中文翻译：

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由YY1调控的CCDC43-ADRM1轴促进胃癌的增殖和转移。

先前的研究表明，包含卷曲螺旋结构域（CCDC）的基因与不同的癌症之间存在关联。我们以前的研究表明CCDC43在结直肠癌中高表达，但是CCDC43在胃癌（GC）中的表达及其分子机制尚待确定。在这里，我们显示CCDC43在胃组织中过表达。CCDC43的表达与肿瘤的分化，淋巴结转移和胃癌的预后密切相关。CCDC43的过表达促进GC细胞的增殖，侵袭和转移。CCDC43可能上调和稳定ADRM1，从而导致泛素介导的蛋白酶体的构建。相反，在体外和体内，抑制ADRM1均可逆转CCDC43在GC中的功能。我们的数据表明，转录因子YY1直接与CCDC43和ADRM1基因启动子结合，导致CCDC43和ADRM1的过表达。此外，体外实验表明，CCDC43或ADRM1的敲低减弱了YY1介导的恶性表型。最后，在临床样本中验证了YY1，CCDC43和ADRM1之间的关联。我们的发现表明，受YY1调控的CCDC43-ADRM1轴可促进GC的增殖和转移，并且该轴可能是GC的潜在治疗靶标。