Expression and functional analysis of TCF4 isoforms in human glioma cells

Transcription factor 4 (TCF4) is a member of the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor family in the Wnt/β‑catenin signaling pathway. The alternative splicing of TCF4 has been reported to exhibit potential carcinogenic properties in various cancer types. In the present study, TCF4 isoforms were cloned and identified in three human glioma cell lines, with the majority of splicing regions being exons 4, 5, 14, 15, and 16. Using MTT assays, it was demonstrated that the overexpression of TCF4 isoforms inhibits the proliferation of U251 cells. Flow cytometry and wound healing analyses revealed that the overexpression of TCF4 isoforms induced cell apoptosis and migration. Taken together, the β‑catenin binding domain of the TCF4 isoforms inhibited cell proliferation, and induced cell apoptosis and migration in glioma. Furthermore, all the isoforms identified contained the N‑terminal part of TCF4 including the β‑catenin binding domain. This implied that a high expression of TCF4 isoforms may lead to Wnt/β‑catenin signal activation and potentially promote malignant glioma development.