Role of basic leucine zipper and W2 domains 2 on the biological behaviors of endometrial cancer cells and its mechanism

Objective To investigate the regulatory effects of basic leucine zipper and W2 domains 2 (BZW2) on proliferation, invasion, migration and cell cycle of endometrial cancer cells and its potential action mechanism.

Methods Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect the expression of BZW2 in human endometrial stromal cell line ESC and human endometrial cancer cells (Ishikawa, KLE, RL95-2, HEC-1-A). BZW2 interference plasmid was transfected into HEC-1-A cells and treated with Wnt/β-catenin signaling pathway agonist SKL2001. CCK-8, clone formation assay, scratch assay and Transwell assay were used to detect cell activity, colony formation, migration and invasion ability, respectively; the cell cycle was detected by flow cytometry; the concentration of BZW2 in Wnt signaling pathway was analyzed by GSEA; the levels of proliferation, metastasis, cycle and Wnt/β-catenin pathway-related proteins were analyzed by Western blot.

Results The expression of BZW2 was up-regulated in endometrial cancer cells, and interference with BZW2 inhibited the proliferation, migration and invasion of endometrial cancer cells, and induced G₀/G₁ cell arrest (P < 0.001). BZW2 knockdown inactivated the Wnt/β-catenin pathway (P < 0.001), and SKL2001 partially reversed the regulatory effects of BZW2 loss on the proliferation, migration, invasion and cell cycle of HEP-1-A cells (P < 0.001).

Conclusion Down-regulation of BZW2 can inhibit the proliferation, invasion and migration of endometrial cancer cells, and promote G₀/G₁ cell arrest, which may be related to the inactivation of Wnt/β-catenin signaling pathway. BZW2 may be a new target for the treatment of endometrial cancer.