Tumor suppressive ZBTB4 inhibits cell growth by regulating cell cycle progression and apoptosis in Ewing sarcoma

Area of Science:

• Oncology
• Molecular Biology
• Cancer Genomics

Background:

• Zinc finger and BTB domain containing 4 (ZBTB4) is increasingly recognized as a tumor suppressor in various human cancers.
• Its role and expression patterns in Ewing sarcoma (ES) remain largely uncharacterized.
• Previous studies link ZBTB4 underexpression to poor patient survival in breast cancer.

Purpose of the Study:

• To investigate the expression of ZBTB4 in Ewing sarcoma (ES) tissues.
• To elucidate the functional role of ZBTB4 in ES cell proliferation, cell cycle, and apoptosis.
• To explore the therapeutic potential of targeting the ZBTB4/Survivin axis in ES.

Main Methods:

• Analysis of Gene Expression Omnibus (GEO) datasets (GSE68776, GSE63157, GSE17679) for ZBTB4 expression in ES versus normal tissues.
• In vitro experiments involving ZBTB4 overexpression in ES cell lines (SK-ES-1, RD-ES) to assess proliferation, cell cycle, and apoptosis.
• In vivo studies using mouse models to evaluate the effect of ZBTB4 restoration on tumor growth.
• Correlation analysis between ZBTB4 and proliferation markers (Ki-67, PCNA) and Survivin expression in ES tissues.

Main Results:

• ZBTB4 expression was significantly lower in ES tissues compared to normal tissues.
• ZBTB4 underexpression correlated with shorter overall and event-free survival in ES patients.
• ZBTB4 overexpression inhibited ES cell proliferation, induced G1 cell cycle arrest, and promoted apoptosis.
• ZBTB4 restoration suppressed tumor growth in vivo and was inversely correlated with Survivin expression.
• Survivin restoration reversed the tumor-suppressive effects of ZBTB4 in ES cells.

Conclusions:

• ZBTB4 functions as a tumor suppressor in Ewing sarcoma (ES).
• ZBTB4 exerts its suppressive role possibly by downregulating Survivin expression.
• The ZBTB4/Survivin axis represents a potential therapeutic target for ES treatment.