Research Center of Basic Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250013, People's Republic of China.
Department of Laboratory Medicine, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, 264200, People's Republic of China.
Dig Dis Sci. 2022 Mar;67(3):904-914. doi: 10.1007/s10620-021-06921-7. Epub 2021 Mar 11.
Differentiated embryonic chondrocyte expressed genes (DECs) are critical regulators of cellular proliferation and differentiation. However, DEC1 and DEC2 as family member have opposite or identical roles in tumor, acting as an "accelerator" or a "brake" in progression.
The possible crosstalk between DEC1 and DEC2 in the gastric cancer (GC).
The association of DEC1 and DEC2 expression with prognosis was investigated by immunohistochemistry. The expression pattern of DECs in GC cells was examined using the CCLE database. DECs knockdown or overexpression was conducted via lentiviral transfection. The proliferation of GC cells was evaluated by CCK8, EdU, and Colony forming. ChIP and luciferase reporter assays were used to verify interaction between DEC1 and the DEC2 promoter. The combination downstream with DEC1 and DEC2 was predicted by bioinformation, with Western blot providing further verification.
We found that reciprocal expression of DEC1 and DEC2 works together to sustain the progression of GC by promoting cell growth. We confirmed this observation in vivo, showing that inhibition DEC1expression could increase DEC2 expression. DEC1 suppresses DEC2 expression by directly binding to the E-box of the DEC2 promoter in GC cells. Furthermore, this regulation of DEC1 on DEC2 enables the further indirect or cooperative activation of additional downstream target genes, MAPK, and STAT3.
Our data demonstrate that DEC1 and DEC2 interact physically and functionally and identify a novel mode of cross-regulatory interaction between DECs that abrogates their functional activity.
分化胚胎软骨细胞表达基因（DEC）是细胞增殖和分化的关键调节因子。然而，DEC1 和 DEC2 作为家族成员，在肿瘤中具有相反或相同的作用，在进展中充当“加速器”或“刹车”。
探讨 DEC1 和 DEC2 在胃癌（GC）中的可能相互作用。
通过免疫组织化学法研究 DEC1 和 DEC2 表达与预后的关系。使用 CCLE 数据库检测 GC 细胞中 DECs 的表达模式。通过慢病毒转染进行 DECs 的敲低或过表达。通过 CCK8、EdU 和集落形成实验评估 GC 细胞的增殖。ChIP 和荧光素酶报告基因检测用于验证 DEC1 和 DEC2 启动子之间的相互作用。通过生物信息学预测 DEC1 和 DEC2 的下游组合，Western blot 进一步验证。
我们发现 DEC1 和 DEC2 的相互表达共同作用，通过促进细胞生长来维持 GC 的进展。我们在体内观察到了这一观察结果，表明抑制 DEC1 表达可以增加 DEC2 表达。在 GC 细胞中，DEC1 通过直接结合 DEC2 启动子的 E 盒抑制 DEC2 表达。此外，DEC1 对 DEC2 的这种调节使它们的下游靶基因 MAPK 和 STAT3 进一步间接或协同激活。
我们的数据表明 DEC1 和 DEC2 具有物理和功能相互作用，并确定了 DECs 之间新的交叉调节相互作用模式，该模式削弱了它们的功能活性。
