Molecular Cancer Guangzhou Medical University Jiang Hua/Xu Ling found a new prognostic marker for acute myeloid leukemia in children

Editor’s note iNature is China’s largest academic official account.
It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, interested parties can Long press or scan the QR code below to follow us
.

iNature circular RNA (circRNA) constitutes a family of transcripts with a unique structure, which has been proven to be essential in tumorigenesis and is a potential biomarker or therapeutic target
.

However, only a few circRNAs have been functionally characterized in childhood acute myeloid leukemia (AML)
.

On October 26, 2021, Jiang Hua and Xu Ling from Guangzhou Medical University published an online publication in Molecular Cancer (IF=27.
40) entitled "CircRNF220, not its linear cognate gene RNF220, regulates cell growth and is associated with relapse in pediatric acute myeloid Leukemia" research paper, which used circRNA microarray to study the expression pattern of circRNA in children with AML
.

The study identified a circRNA, circRNF220, which is particularly abundant and accumulated in the peripheral blood and bone marrow of pediatric AML patients
.

It can distinguish AML from ALL and other hematological malignancies with high sensitivity and specificity
.

It is worth noting that the expression of circRNF220 independently predicts the prognosis, and the high expression of circRNF220 is an unfavorable prognostic marker of recurrence
.

In addition, this study characterized the function of circRNF220 and found that circRNF220 knockdown specifically inhibits the proliferation of AML cell lines and primary cells and promotes apoptosis
.

In terms of mechanism, circRNF220 may act as the endogenous sponge of miR-30a to isolate miR-30a and inhibit its activity, thereby increasing the expression of its targets MYSM1 and IER2 and being related to the recurrence of AML
.

In conclusion, this study shows that circRNF220 can efficiently and specifically diagnose pediatric AML, which has an impact on the prediction of recurrence
.

Acute myeloid leukemia (AML) is a relatively rare malignant tumor among childhood malignancies, accounting for less than one-fifth of acute leukemia cases diagnosed in childhood
.

However, compared with pediatric acute lymphoblastic leukemia (ALL), it is still a challenging disease with a poor prognosis
.

Although the diagnosis and treatment of AML have made great progress in the past few decades, approximately 40% of children with AML will experience short-term relapses
.

In AML, some risk factors, such as age, cytogenetic characteristics, white blood cell count (WBC), and minimal residual disease (MRD), are currently used for prognosis
.

However, the predictive value of these assessed covariates is limited and has been commonly reported in adults
.

It has rarely been evaluated in the pediatric patient population
.

Therefore, not only accurate and timely diagnosis, but also valuable prognostic biomarkers and new treatment algorithms are essential for the clinical management of pediatric AML.

.

Circular RNA (circRNA) is a covalently closed non-linear RNA molecule produced by reverse splicing of precursor mRNA, and has been considered a defective splicing product for decades
.

However, it has become obvious that circRNAs are functional entities
.

It is worth noting that most circRNAs are composed of different numbers of constitutive exons, which are extremely stable RNA molecules with cell type or tissue type specific expression patterns
.

Due to their biological properties and their involvement in tumorigenesis through multiple mechanisms, such as microRNA (miRNA) sponge, RNP binding or as a translation template, circRNAs play a potential role as biomarkers in various cancers
.

Emerging evidence indicates that the role of some circRNAs in AML has been established
.

For example, circ-ANXA2 is upregulated in AML, and its knockdown (KD) inhibits proliferation, enhances apoptosis, and increases the chemosensitivity of THP-1 and KG-1 cells by acting as an effective microRNA sponge for miR-23a-5p
.

CircPAN3 was confirmed to mediate adriamycin resistance in AML cells by targeting miR-153-5p/miR-183-5p/XIAP axis and enhancing autophagy activity
.

However, it is worth noting that little is known about the regulatory effects of circRNA in children with AML
.

Here, the study attempts to explore the regulatory role of circRNA in children with AML
.

This study determined that circRNF220, a circRNA derived from the RING domain E3 ubiquitin ligase gene RNF220, is specifically up-regulated in pediatric AML and is required for the progression of AML
.

CircRNF220 KD significantly hinders the activity of primary pediatric AML cells
.

In addition, the study found that circRNF220 can play its regulatory function as a competitive endogenous RNA by binding miR-30a and then regulating the expression of downstream genes
.

Importantly, the study found that circRNF220 is not only superior to current markers in terms of its high sensitivity, specificity and diagnostic simplicity, but also proved the prognostic value of early recurrence by evaluating bone marrow (BM) and even peripheral blood (PB) samples
.

Reference message: https://molecular-cancer.
biomedcentral.
com/articles/10.
1186/s12943-021-01395-7