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Reciprocal Expression of Differentiated Embryonic Chondrocyte Expressed Genes Result in Functional Antagonism in Gastric Cancer

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Abstract

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.

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Acknowledgments

This study was financially supported by the National Natural Science Foundation of China (Nos. 31671468 and 31970728), the Academic promotion programme of Shandong First Medical University (No. 2019QL024), the Shandong Provincial Natural Science Foundation of China (Nos. ZR2016HM15and ZR2018MH021)

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Author notes

  1. Binbin Li and Yan Chu have contributed equally to this work.

Authors and Affiliations

  1. Research Center of Basic Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250013, People’s Republic of China

    Binbin Li, Yan Chu, Xiaoli Ma, Duanrui Liu, Shanglin Wang, Yunshan Wang & Yanfei Jia

  2. Department of Laboratory Medicine, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, 264200, People’s Republic of China

    Binbin Li

  3. Departments of General Surgery, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250013, People’s Republic of China

    Bing Yan

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  1. Binbin Li
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Correspondence to Yanfei Jia.

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Western blot analysis demonstrated that DECs regulate AKT and NF-κB expression (TIF 37 KB)

10620_2021_6921_MOESM2_ESM.tif

Real-time PCR analysis of DEC1 and DEC2 expression in DEC1 silenced or overexpression and DEC2 overespression GC cells. EV, empty vector; over, overexpression. Data are represented as the means ± SD. *P < 0.05 (TIF 309 KB)

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Li, B., Chu, Y., Yan, B. et al. Reciprocal Expression of Differentiated Embryonic Chondrocyte Expressed Genes Result in Functional Antagonism in Gastric Cancer. Dig Dis Sci 67, 904–914 (2022). https://doi.org/10.1007/s10620-021-06921-7

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