FOXD3 may be a new cellular target biomarker as a hypermethylation gene in human ovarian cancer

Abstract

Background FOXD3 is aberrantly regulated in several tumors, but its underlying mechanisms in ovarian cancer (OC) remains largely unknown. The present study aimed to explore the role and associated mechanisms of FOXD3 in OC. Methods Microarray data from GEO was used to analyze differential CpG sites and differentially methylated regions (DMR) in tumor tissues and Illumina 450 genome-wide methylation data was employed. The FOXD3 expression level was determined through qRT-PCR and western blot analysis. Wound healing test, colony formation and flow cytometry assay were utilized to analyze cell migration, proliferation abilities, cell cycle and cell apoptosis, respectively. Finally, the effect of FOXD3 on tumor growth was investigated through in vivo xenograft experiments. Results GEO data analysis showed that FOXD3 was hypermethylated in OC tissues. Also, qRT-PCR revealed that FOXD3 was low expressed and methylation-specific PCR (MSP) confirmed that the methylation level of FOXD3 was hypermethylated. Combined treatment of 5-aza-2′-deoxycytidine (5-Aza-dC) could synergistically restored FOXD3 expression. Finally, in vitro and in vivo experiments showed that demethylated FOXD3 decreased cell proliferation and migration abilities, and increased the cell apoptosis. In vivo experiment detected that demethylated FOXD3 restrained tumor growth. Conclusions FOXD3 could act as a tumor suppressor to inhibit cell proliferation, migration and promote cell apoptosis in OC cells. Electronic supplementary material The online version of this article (10.1186/s12935-019-0755-8) contains supplementary material, which is available to authorized users.

Epigenetic Biomarkers in the Management of Ovarian Cancer: Current Prospectives

“…Another finding suggests that promoter methylation of RASSF1A, APC, GSTP1, and MGMT correlates with the presence of invasive ovarian carcinomas (Makarla et al, 2005). Hypermethylation of FOXD3 correlated with tumor suppressive role (inhibition of proliferation, migration and promotion of apoptosis) in ovarian cancer cells and thus could serve as a potential therapeutic target for diagnosis of ovarian cancer (Luo et al, 2019).…”

FOXD3 confers chemo-sensitivity in ovarian cancer through a miR-335/DAAM1/myosin II axis-dependent mechanism

“…Initial results indicated that overexpression of FOXD3 could promote the apoptosis while inhibiting the proliferation and chemoresistance of OC cells. FOXD3 is poorly expressed in OC tissues while its overexpression weakens OC cell proliferating and migrating ability and increases cell apoptosis while restraining tumor growth in vivo [ 17 ]. FOXD3 expression is downregulated in CP-resistant nasopharyngeal carcinoma cells and it can promote the expression of miR-26b which sensitizes nasopharyngeal carcinoma cells to CP [ 7 ].…”

Understanding Transcriptomic and Serological Differences between Forced Molting and Natural Molting in Laying Hens

“…Chordate embryonic development (FOXD3, WT1, BRCA1, and BRCA2) was enriched in DEGs in the ovaries. Demethylated FOXD3 decreases cell migration and proliferation abilities and increases cell apoptosis, even in ovarian cancer [ 36 ]. FOXD3 was more lowly expressed in FM_1 potentially contributing to accelerated cell aging, while the other three genes were higher expressed in FM_1.…”