Ppm1d truncating mutations promote the development of genotoxic stress-induced AML DOI Creative Commons
Monika Burócziová, Petr Daněk, Anna Oravetzova

et al.

Leukemia, Journal Year: 2023, Volume and Issue: 37(11), P. 2209 - 2220

Published: Sept. 14, 2023

Abstract Hematopoietic stem cells (HSCs) ensure blood cell production during the life-time of an organism, and to do so they need balance self-renewal, proliferation, differentiation, migration in a steady state as well response stress or injury. Importantly, aberrant proliferation HSCs leads hematological malignancies, thus, tight regulation by various tumor suppressor pathways, including p53, is essential. Protein phosphatase magnesium-dependent 1 delta (PPM1D) negative regulator p53 promotes survival upon induction genotoxic stress. Truncating mutations last exon PPM1D lead stable, enzymatically active protein are commonly associated with clonal hematopoiesis. Using transgenic mouse model, we demonstrate that truncated reduces self-renewal basal conditions but development aggressive AML after exposure ionizing radiation. Inhibition suppressed colony growth leukemic progenitor carrying PPM1D, remarkably, it provided protection against irradiation-induced growth. Altogether, affects HSC maintenance, disrupts normal hematopoiesis, its inhibition could be beneficial context therapy-induced AML.

Language: Английский

IGF2BP3-stabilized CAMK1 regulates the mitochondrial dynamics of renal tubule to alleviate diabetic nephropathy DOI Creative Commons

Yuan Du,

Hao Li,

Wenni Dai

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1870(3), P. 167022 - 167022

Published: Jan. 11, 2024

Language: Английский

Citations

6
Dynamics of N6‐methyladenosine modification during aging and their potential roles in the degeneration of intervertebral disc DOI Creative Commons
Libangxi Liu,

Hong Sun,

Yang Zhang

et al.

JOR Spine, Journal Year: 2024, Volume and Issue: 7(1)

Published: Jan. 25, 2024

Abstract Background The N6‐methyladenosine (m6A) dynamics in the progression of intervertebral disc (IVD) aging remain largely unknown. This study aimed to explore distribution and pattern m 6 A modification nucleus pulpous (NP) tissues rats at different ages. Methods Histological staining MRI were performed evaluate degeneration IVD. expression m6A modifiers was analyzed using qRT‐PCR western blot. Subsequently, methylated RNA immunoprecipitation next generation sequencing RNA‐seq conducted identify differences methylome transcriptome NP tissues. Results Compared 2‐month‐old rats, we found significant changes global level Mettl3 FTO from 20‐month‐old rats. During aging, there 1126 persistently differentially peaks within 931 genes, 51 expressed genes. GO KEGG analyses showed that these modified genes mainly engaged biological processes pathways degermation (IDD), such as extracellular matrix metabolism, angiogenesis, inflammatory response, mTOR AMPK signaling pathways. Meanwhile, conjoint Venn diagram revealed a total 405 related contained methylation levels contrast 10‐month‐old Moreover, it four with hypermethylated including BUB1, CA12, Adamts1, Adamts4 depicted protein level, which BUB1 CA12 decreased, while Adamts1 increased during aging. Conclusion Collectively, this elucidated Furthermore, involved IDD These findings may provide novel insights into mechanisms therapies perspective

Language: Английский

Citations

6
Phytic acid promotes high glucose-mediated bone marrow mesenchymal stem cells osteogenesis via modulating circEIF4B that sponges miR-186-5p and complexes with IGF2BP3 DOI
Jin Wu, Xiang Li, He-Peng Nie

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 222, P. 116118 - 116118

Published: March 11, 2024

Language: Английский

Citations

6
Reading the m6A-encoded epitranscriptomic information in development and diseases DOI Creative Commons

Yunbing Chen,

Ziyu Zhou, Yanxi Chen

et al.

Cell & Bioscience, Journal Year: 2024, Volume and Issue: 14(1)

Published: Sept. 28, 2024

Abstract N 6 -methyladenosine (m A) represents the most prevalent internal and reversible modification on RNAs. Different cell types display their unique m A profiles, which are determined by functions of writers erasers. M modifications lead to different outcomes such as decay, stabilization, or transport The A-encoded epigenetic information is interpreted readers interacting proteins. essential for biological processes, defects in have been discovered diverse diseases. Here, we review latest advances roles development These recent studies not only highlight importance regulating fate transitions, but also point potential application drugs targeting

Language: Английский

Citations

6
Ppm1d truncating mutations promote the development of genotoxic stress-induced AML DOI Creative Commons
Monika Burócziová, Petr Daněk, Anna Oravetzova

et al.

Leukemia, Journal Year: 2023, Volume and Issue: 37(11), P. 2209 - 2220

Published: Sept. 14, 2023

Abstract Hematopoietic stem cells (HSCs) ensure blood cell production during the life-time of an organism, and to do so they need balance self-renewal, proliferation, differentiation, migration in a steady state as well response stress or injury. Importantly, aberrant proliferation HSCs leads hematological malignancies, thus, tight regulation by various tumor suppressor pathways, including p53, is essential. Protein phosphatase magnesium-dependent 1 delta (PPM1D) negative regulator p53 promotes survival upon induction genotoxic stress. Truncating mutations last exon PPM1D lead stable, enzymatically active protein are commonly associated with clonal hematopoiesis. Using transgenic mouse model, we demonstrate that truncated reduces self-renewal basal conditions but development aggressive AML after exposure ionizing radiation. Inhibition suppressed colony growth leukemic progenitor carrying PPM1D, remarkably, it provided protection against irradiation-induced growth. Altogether, affects HSC maintenance, disrupts normal hematopoiesis, its inhibition could be beneficial context therapy-induced AML.

Language: Английский

Citations

12