RNA m<sup>6</sup>A reader YTHDF2 facilitates precursor miR-126 maturation to promote acute myeloid leukemia progression

Zheng Zhang; Keren Zhou; Li Han; Andrew Small; Jianhuang Xue; Huilin Huang; Hengyou Weng; Rui Su; Brandon Tan; Chao Shen; Wei Li; Zhicong Zhao; Ying Qing; Xi Qin; Kitty Wang; Keith Leung; Mark Boldin; Chun-Wei Chen; David Ann; Zhijian Qian

doi:10.1016/j.gendis.2023.01.016

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RNA m⁶A reader YTHDF2 facilitates precursor miR-126 maturation to promote acute myeloid leukemia progression

Full-length article | 更新时间：2024-02-04

- RNA m⁶A reader YTHDF2 facilitates precursor miR-126 maturation to promote acute myeloid leukemia progression
- Genes & Diseases Vol. 1, Issue 1, Pages: 382-396(2024)
- 作者机构：
  
  1. Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia,CA,USA,91016
  2. Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Duarte,CA,USA,91010
  3. School of Pharmacy, China Medical University,Liaoning,Shenyang,China,110001
  4. Tongji Hospital Affiliated to Tongji University, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University,Shanghai,China,200092
  5. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine,Guangdong,Guangzhou,China,510060
  6. Guangzhou Laboratory,Guangdong,Guangzhou,China,510005
  7. Bioland Laboratory,Guangdong,Guangzhou,China,51005
  8. Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine,Shanghai,China,200127
  9. Department of Diabetes Complications and Metabolism, Beckman Research Institute of City of Hope, Duarte,CA,USA,91010
  10. Department of Biochemistry and Molecular Biology, University of Florida, Gainesville,FL,USA,32603
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2023.01.016
  CLC：
- Published：2024，
  
  Published Online：1 January 2024，
扫描看全文
Zheng Zhang, Keren Zhou, Li Han, et al. RNA m⁶A reader YTHDF2 facilitates precursor miR-126 maturation to promote acute myeloid leukemia progression. [J]. Genes & Diseases 1(1):382-396(2024)
DOI：

Zheng Zhang, Keren Zhou, Li Han, et al. RNA m⁶A reader YTHDF2 facilitates precursor miR-126 maturation to promote acute myeloid leukemia progression. [J]. Genes & Diseases 1(1):382-396(2024) DOI： 10.1016/j.gendis.2023.01.016.

摘要

Abstract

the most common internal modification of mRNA

-methyladenosine (m

A) and its regulators modulate gene expression and play critical roles in various biological and pathological processes including tumorigenesis. It was reported previously that m

A methyltransferase (writer)

methyltransferase-like 3 (METTL3) adds m

A in primary microRNAs (pri-miRNAs) and facilitates its processing into precursor miRNAs (pre-miRNAs). However

it is unknown whether m

A modification also plays a role in the maturation process of pre-miRNAs and (if so) whether such a function contributes to tumorigenesis. Here

we found that YTHDF2 is aberrantly overexpressed in acute myeloid leukemia (AML) patients

especially in relapsed patients

and plays an oncogenic role in AML. Moreover

YTHDF2 promotes expression of miR-126-3p (also known as miR-126

as it is the main product of precursor miR-126 (pre-miR-126))

a miRNA that was reported as an oncomiRNA in AML

through facilitating the processing of pre-miR-126 into mature miR-126. Mechanistically

YTHDF2 recognizes m

A modification in pre-miR-126 and recruits AGO2

a regulator of pre-miRNA processing

to promote the maturation of pre-miR-126.

YTHDF2

positively and negatively correlates with miR-126 and miR-126's downstream target genes

respectively

in AML patients

and forced expression of miR-126 could largely rescue

YTHDF2/Ythdf2

depletion-mediated suppression on AML cell growth/proliferation and leukemogenesis

indicating that miR-126 is a functionally important target of YTHDF2 in AML. Overall

our studies not only reveal a previously unappreciated YTHDF2/miR-126 axis in AML and highlight the therapeutic potential of targeting this axis for AML treatment

but also suggest that m

A plays a role in pre-miRNA processing that contributes to tumorigenesis.

关键词

Keywords

AMLmiR-126N6-methyladenosinePre-miRNA maturationYTHDF2

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RNA m6A reader YTHDF2 facilitates precursor miR-126 maturation to promote acute myeloid leukemia progression

DOI：10.1016/j.gendis.2023.01.016

摘要

Abstract

关键词

Keywords

references

RNA m⁶A reader YTHDF2 facilitates precursor miR-126 maturation to promote acute myeloid leukemia progression