Biology of the Cell

SOX15 Transcriptionally Decreases the Level of MMP2 and Inhibits Vasculogenic Mimicry to Slow Down the Progression of Ovarian Cancer

ABSTRACTBackground InformationVascular mimicry (VM) is pivotal for promoting tumor cell proliferation and invasion in ovarian (OV) cancer patients. Sex‐determining region Y‐box 15 (SOX15) suppresses the malignant growth of tumor cells. However, the function of SOX15 in OV cancer remains undefined. Using SKOV‐3 and ES2 cell lines, along with xenograft models in nude mice, we investigated the effects of SOX15 on tumor cell growth and VM formation in OV cancer, as well as the underlying mechanisms.ResultsWe found that SOX15 inhibited the proliferation, migration, and invasion of SKOV‐3 cells. SOX15 overexpression reduced VM formation in SKOV‐3 cells, accompanied by decreased levels of VE‐cadherin and vascular endothelial growth factor A (VEGFA). Similarly, SOX15 suppressed ES2 cell proliferation and motility. Additionally, xenograft experiments demonstrated that SOX15 knockdown increased tumor volume in mice, along with upregulated expression of Ki67 and matrix metalloproteinase‐2 (MMP2) in tumor tissues. CD31/PAS double staining revealed that silencing SOX15 promoted VM formation in tumors. Mechanistically, SOX15 overexpression downregulated MMP2 at both mRNA and protein levels, suppressing VM formation and thereby slowing OV cancer progression. Dual‐luciferase reporter assays revealed that SOX15 overexpression inhibited MMP2 promoter activity, and chromatin immunoprecipitation followed by PCR (ChIP‐PCR) confirmed the direct binding of SOX15 to the MMP2 promoter.ConclusionsOur results indicate that SOX15 transcriptionally represses MMP2 expression, thereby inhibiting VM formation and ultimately suppressing OV cancer initiation and progression.SignificanceWe establish a theoretical foundation for developing novel therapeutic approaches targeting the SOX15/MMP2 axis in OV cancer treatment.

Transcriptional Activation of EGFL6 by E2F8 Promotes Proliferation, Migration, and Invasion in Endometrial Carcinoma Cell

ABSTRACT Background Endometrial cancer (EC) posed a great threat to women's health, especially in postmenopausal women. E2F transcription factor 8 (E2F8), recognized as a central regulator of critical cellular processes, is overexpressed in endometrial carcinomas. However, the underlying mechanisms remains elusive and worthy of further investigation. Herein, we investigated whether E2F8 activates the expression of epidermal growth factor‐like domain multiple 6 (EGFL6) through transcriptional regulatory mechanisms to regulate the occurrence and development of EC tumors. Methods Western blot and quantitative reverse transcription polymerase chain reaction (qPCR) analyses revealed the expression profiles of E2F8 and EGFL6 in tumor tissues and EC cells. The Ishikawa and KLE cell lines were selected as in vitro models of EC and were subsequently transfected with sh‐E2F8 or overexpression EGFL6 (oe‐EGFL6) plasmids. CCK‐8 assay and Transwell assay were performed to evaluate the cell viability, migration, and invasion of EC cells. A dual luciferase assay was conducted to assess the interaction between E2F8 and EGFL6. E2F8‐knockdown Ishikawa cells were subcutaneously transplanted to investigate their effect on EC tumor growth. Results E2F8 was greatly upregulated in EC cells. Silencing E2F8 inhibits the proliferation, migration, and invasion of EC cells, thereby suppressing tumor growth in vivo. Mechanistically, E2F8 transcriptionally activates EGFL6 by binding to its promoter. oe‐EGFL6 rescues the impacts of E2F8 silencing on the proliferation, migration, and invasion of EC cells. Conclusion These results indicated that E2F8 promotes proliferation, migration, and invasion of EC cells by transcriptionally activating EGFL6.