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Erschienen in:
11.03.2021 | Original Article
Reciprocal Expression of Differentiated Embryonic Chondrocyte Expressed Genes Result in Functional Antagonism in Gastric Cancer
Erschienen in: Digestive Diseases and Sciences | Ausgabe 3/2022
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Background
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.
Aims
The possible crosstalk between DEC1 and DEC2 in the gastric cancer (GC).
Methods
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.
Results
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.
Conclusion
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.