RUNX transcription factors: biological functions and implications in cancer

Abstract

Runt-related transcription factors (RUNX) are a family of transcription factors that are essential for normal and malignant hematopoietic processes. Their most widely recognized role in malignancy is to promote the occurrence and development of acute myeloid leukemia. However, it is worth noting that during the last decade, studies of RUNX proteins in solid tumors have made considerable progress, suggesting that these proteins are directly involved in different stages of tumor development, including tumor initiation, progression, and invasion. RUNX proteins also play a role in tumor angiogenesis, the maintenance of tumor cell stemness, and resistance to antitumor drugs. These findings have led to the consideration of RUNX as a tumor biomarker. All RUNX proteins are involved in the occurrence and development of solid tumors, but the role of each RUNX protein in different tumors and the major signaling pathways involved are complicated by tumor heterogeneity and the interacting tumor microenvironment. Understanding how the dysregulation of RUNX in tumors affects normal biological processes is important to elucidate the molecular mechanisms by which RUNX affects malignant tumors.

Keywords: Angiogenesis; Drug resistance; RUNX family; Signaling pathways; Tumor cell stemness; Tumor microenvironment.

Fig. 1

Pan-cancer assessment of RUNX family members' expression in comparison with normal tissues, sourced from the TCGA and GTEx databases. The violin plots consistently illustrate differences between normal tissues (depicted in orange) and tumor samples (depicted in gray). A RUNX1, B RUNX2, and C RUNX3 expression variations among different malignancies. *P < 0.05, **P < 0.01, ***P < 0.001

Fig. 2

Prognostic implications of RUNX family gene expressions in various cancers. A RUNX1, B RUNX2, and C RUNX3: Kaplan–Meier curves depict the correlation of high RUNX expression (in red) with overall survival (OS). Data sourced from the Kaplan–Meier plotter database. P-values and hazard ratios (HR) were calculated using the logrank test to indicate the statistical significance of the survival outcomes

Fig. 3

Comprehensive roles of RUNX family genes in oncogenesis. The diagram explicitly highlights the pivotal functions of RUNX genes across diverse cancer hallmarks, emphasizing the RUNX-associated effects on cellular proliferation and invasion, metastatic dissemination, angiogenesis, chemoresistance, and maintenance and self-renewal of cancer stem cells