Blood | Significant progress!

iNatureRNA binding protein (RBP) is a key regulator of transcription and translation, and is often dysregulated in cancer.

Although it is increasingly believed that RBP is important for normal hematopoiesis and hematological malignancies as oncogenes or tumor suppressors, the mechanism by which RBP maintains leukemia is still elusive.

On March 24, 2021, Zhang Haojian’s team from Wuhan University published an online research paper entitled "YBX1 is required for maintaining myeloid leukemia cell survival by regulating BCL2 stability in an m6A-dependent manner" in Blood (IF=17.
53).
The research showed YBX1 is unique to maintain the survival of myeloid leukemia cells in an m6A-dependent manner.

The study found that the expression of YBX1 was significantly up-regulated in myeloid leukemia cells, while in vitro and in vivo, the loss of YBX1 significantly induced apoptosis, promoted differentiation, and reduced primary human and mouse acute myeloid leukemia (AML) cells Proliferation and damage the ability of leukemia.

The loss of YBX1 will not significantly affect normal hematopoietic function.

In terms of mechanism, YBX1 interacts with IGF2BP and stabilizes m6A-tagged RNA.

In addition, YBX1 lacks regulation of the expression of apoptosis-related genes and promotes the mRNA decay of MYC and BCL2 in an m6A-dependent manner, which is attributed to poor survival caused by YBX1 deletion.

Therefore, the findings of this study reveal the selective and critical role of YBX1 in maintaining the survival of myeloid leukemia, which may provide a theoretical basis for the targeted therapy of YBX1 in myeloid leukemia.

Eukaryotic cells regulate mRNA expression through transcription and post-transcriptional mechanisms.

In these processes, RNA binding protein (RBP) plays an important role by fine-tuning gene expression, RNA splicing, polyadenylation, stability, localization, translation and degradation.

RBP usually binds RNA via one or more RNA binding domains (RBD) such as RNA recognition motifs (RRM), DEAD box domains or K homology domains (KH).

Recent advances have found that other RBPs that lack conventional RBD have been involved in different human cancers.
Therefore, it is necessary to understand the complex regulatory mechanisms of RBPs and their cancer-related RNA targets, which will provide a better understanding of cancer biology.
Understand and uncover potential treatment goals.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by the uncontrolled expansion of poorly differentiated bone marrow cells.

Accumulated evidence shows that RBP is essential for normal hematopoietic and hematopoietic malignancies.

For example, frequent mutations of RBP have been identified as splicing factors in myeloid dysplasia.

m6A is a ubiquitous modification of mammalian mRNA and plays a key role in determining the fate of RNA.

This modification is reversible and is catalyzed by the methyltransferase complex (METTL3-METTL14-WTAP) and the demethylase ALKBH5 and FTO.

Several key m6A modulators have become key players in normal and malignant hematopoietic processes.

The RNA m6A demethylase ALKBH5 is necessary to maintain the function of AML LSCs, but normal hematopoietic stem cells (HSCs) are not.

Despite these recent advances, it is still necessary to explore the basic RBP in the maintenance and survival of leukemia, which will help understand the pathogenesis of AML.

YBX1 belongs to the RBP family and is a multifunctional protein containing an evolutionarily conserved cold-shock domain.

YBX1 participates in various biological processes by affecting a wide range of genes involved in cell proliferation, survival, drug resistance and chromatin destabilization.

YBX1 can also serve as a universal oncoprotein, which is necessary for tumor cell proliferation, progression and metastasis.

However, the role of YBX1 in leukemia remains elusive.

Here, the study showed that YBX1 regulates the stability of m6A-labeled mRNA by interacting with IGF2BPs, and is necessary for the survival of myeloid leukemia cells.

This study showed that YBX1 is unique to maintain the survival of myeloid leukemia cells in an m6A-dependent manner.

The study found that the expression of YBX1 was significantly up-regulated in myeloid leukemia cells, while in vitro and in vivo, the loss of YBX1 significantly induced apoptosis, promoted differentiation, and reduced primary human and mouse acute myeloid leukemia (AML) cells Proliferation and damage the ability of leukemia.

The loss of YBX1 will not significantly affect normal hematopoietic function.

The article pattern (picture from Blood).
From the mechanism, YBX1 interacts with IGF2BP and stabilizes the m6A-tagged RNA.

In addition, YBX1 lacks regulation of the expression of apoptosis-related genes and promotes the mRNA decay of MYC and BCL2 in an m6A-dependent manner, which is attributed to poor survival caused by YBX1 deletion.

Therefore, the findings of this study reveal the selective and critical role of YBX1 in maintaining the survival of myeloid leukemia, which may provide a theoretical basis for the targeted therapy of YBX1 in myeloid leukemia.

Reference message: https://ashpublications.
org/blood/article-abstract/doi/10.
1182/blood.
2020009676/475592/YBX1-is-required-for-maintaining-myeloid-leukemia?redirectedFrom=fulltext