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. 2024 Dec 31;25(1):2299288.
doi: 10.1080/15384047.2023.2299288. Epub 2024 Jan 4.

WYC-209 inhibited GC malignant progression by down-regulating WNT4 through RARα

Zhenyuan Qian  1 , Wenfa Lin  2 , Xufan Cai  2 , Jianzhang Wu  1 , Kun Ke  1 , Zaiyuan Ye  1 , Fang Wu  1
Affiliations

WYC-209 inhibited GC malignant progression by down-regulating WNT4 through RARα

Zhenyuan Qian et al. Cancer Biol Ther. .

Abstract

Gastric cancer (GC) has been a major health burden all over the world but there are fewer promising chemotherapeutic drugs due to its multidrug resistance. It has been reported that WYC-209 suppresses the growth and metastasis of tumor-repopulating cells but the effect on GC was not explored. MTT, colony formation, and transwell assays were performed to examine the effects of WYC-209 on the proliferation, colony growth, and mobility of GC cells. Western blotting and qRT-PCR were used to detect the expression of proteins and mRNA. RNA-seq and enrichment analyses were conducted for the differentially expressed genes and enriched biological processes and pathways. The rescue experiments were carried out for further validation. Besides, we constructed xenograft model to confirm the effect of WYC-209 in vivo. The dual-luciferase reporter and Chromatin immunoprecipitation were implemented to confirm the underlying mechanism. WYC-209 exerted excellent anti-cancer effects both in vitro and in vivo. Based on RNA-seq and enrichment analyses, we found that Wnt family member 4 (WNT4) was significantly down-regulated. More importantly, WNT4 overexpression breached the inhibitory effect of WYC-209 on GC progression. Mechanically, WYC-209 significantly promoted the binding between retinoic acid receptor α (RARα) and WNT4 promoter. WYC-209 exerts anti-tumor effects in GC by down-regulating the expression of WNT4 via RARα.

Keywords: GC; RARα; WNT4; WYC-209; synthetic retinoid.

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Conflict of interest statement

No potential conflict of interest was reported by the authors.

Figures

Figure 1.
Figure 1.
WYC-209 inhibited the cell survival, proliferation, colony growth, and motility of GC cells.
Figure 2.
Figure 2.
WYC-209 suppressed EMT and tumor progression.
Figure 3.
Figure 3.
WYC-209 induced the heterotypic down-regulation of WNT4.
Figure 4.
Figure 4.
Overexpressing WNT4 breached the inhibitory effect of WYC-209 on cell proliferation, colony-forming, and motility.
Figure 5.
Figure 5.
EMT and tumor progression inhibited by WYC-209 were abrogated by overexpressing WNT4.
Figure 6.
Figure 6.
WYC-209 inhibited GC progression by down-regulating WNT4 via RARα.
See this image and copyright information in PMC

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References

    1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D.. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–12. doi:10.3322/caac.20107. - DOI - PubMed
    1. Correa P. Gastric cancer: overview. Gastroenterol Clin North Am. 2013;42(2):211–7. doi:10.1016/j.gtc.2013.01.002. - DOI - PMC - PubMed
    1. Sitarz R, Skierucha M, Mielko J, Offerhaus GJA, Maciejewski R, Polkowski WP. Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer Manag Res. 2018;10:239–248. doi:10.2147/CMAR.S149619. - DOI - PMC - PubMed
    1. Oh DY, Bang YJ. Adjuvant and neoadjuvant therapy for gastric cancer. Curr Treat Options Oncol. 2013;14(3):311–20. doi:10.1007/s11864-013-0238-4. - DOI - PubMed
    1. Sun SY, Lotan R. Retinoids and their receptors in cancer development and chemoprevention. Crit Rev Oncol Hematol. 2002;41(1):41–55. doi:10.1016/s1040-8428(01)00144-5. - DOI - PubMed

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