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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. [ABSTRACT FROM AUTHOR]

Oxaliplatin is a member of the platinum group that is often used to treat glioma, a common type of malignant brain tumor, though it does not come with desirable and notable effects. This study attempted to investigate how ELK3 impacts the oxaliplatin resistance of glioma cells and its molecular mechanism. Bioinformatics analysis was employed to screen mRNAs with differential expression in glioma cells and predict the possible regulator downstream. We used qRT-PCR to detect the expression of ELK3 and RNASEH2A. Dual-luciferase and ChIP assays were adopted to reassure the regulatory relationship between the two. We also evaluated cell viability and sphere formation efficiency through CCK-8 and sphere formation assay and calculated the IC50 value by using CCK-8 assay. The expression of stemness-related proteins (ALDH1 and Nanog) was assessed through western blot. Glioma cells and tissues presented a significantly high expression of ELK3, the knock-down of which would reduce the cell viability, stemness and oxaliplatin resistance dramatically. Bioinformatics analysis predicted RNASEH2A to be the downstream regulator of ELK3. RNASEH2A was remarkably upregulated in glioma tissue and cells. The results from dual luciferase assay and ChIP experiment verified the binding relationship between RNASEH2A promoter region and ELK3. Then through rescue experiments, we confirmed that overexpression of RNASEH2A could compensate for the inhibition of glioma cell progression resulting from the knock-down of ELK3. ELK3 could promote stemness and oxaliplatin resistance of glioma cells by upregulating RNASEH2A, indicating that targeting ELK3/RNASEH2A axis may be a possible solution to overcome oxaliplatin resistance of glioma cells. [ABSTRACT FROM AUTHOR]