Upregulation of ZEB1-Derived Circular RNAs Is Associated with SF3B1-Mutated Myelodysplastic Neoplasms

Abstract

Myelodysplastic neoplasms (MDS) are a heterogeneous group of bone marrow (BM) disorders characterized by ineffective hematopoiesis, peripheral cytopenia, and increased tendency to leukemic transformation. Mutations of splicing factor gene SF3B1 are frequently found in MDS, resulting in aberrant splicing of multiple genes such as those involved in mitochondrial metabolism.

Splicing process results not only in a variety of linear mRNAs but it can also produce covalently enclosed RNAs, circular RNAs (circRNAs). CircRNAs regulate biological processes through various molecular mechanisms, e.g. miRNA sponging.

CircRNAs are deregulated in many types of cancer, including MDS. Based on our previous data (Dostalova Merkerova M, et al., Cancer Genomics Proteomics. 2022; 19:205-228), we hypothesized that there is an association between MDS and the level of circRNAs derived from ZEB1 gene.

ZEB1 is an essential hematopoietic transcription factor governing blood lineage commitment. Here, we studied expression and function of these circRNAs in SF3B1-mutated MDS.