TCF21: a critical transcription factor in health and cancer

Transcription factor 21 (TCF21) is a member of the basic helix-loop-helix (bHLH) transcription factors that mediate cell fate and differentiation by orchestrating temporal and spatial gene expression during the development of various organs. It plays a crucial role in a wide spectrum of biological processes, including organogenesis, epithelial-mesenchymal transition (EMT), cell cycle, autophagy, proliferation, differentiation, specification, maturation, and survival of cells, as well as invasion and metastasis of cancer cells. Controlled expression and activity of TCF21 provide a balanced transcriptional program that guarantees appropriate growth and maturation during embryogenesis and organ development. Its dysregulation is closely correlated with a variety of diseases, including cancer. Its function is mainly regulated by non-coding RNAs (ncRNAs), post-translational modifications (PTMs), and protein-protein interactions. However, the exact mechanisms of TCF21 dysregulation in disease progression are still elusive. This review summarizes the regulatory mechanisms of TCF21 expression and activity and highlights its critical role in health and disease. This information may contribute to the development of better diagnostics and treatments for cancer and other developmental diseases.