Melatonin antagonizes bone loss induced by mechanical unloading via IGF2BP1-dependent m6A regulation

Cellular and Molecular Life Sciences, Год журнала: 2025, Номер 82(1)

Опубликована: Янв. 23, 2025

Disuse bone loss is prone to occur in individuals who lack mechanical stimulation due prolonged spaceflight or extended bed rest, rendering them susceptible fractures and placing an enormous burden on social care; nevertheless, the underlying molecular mechanisms of caused by unloading have not been fully elucidated. Numerous studies focused epigenetic regulation disuse loss; yet limited research has conducted impact RNA modification formation response conditions. In this study, we discovered that m6A reader IGF2BP1 was downregulated both osteoblasts treated with 2D clinostat tissue HLU mice. Supplementing could promote osteoblast proliferation partially alleviate adverse effects formation. Mechanistically, inhibited degradation Lef1 mRNA directly binding its recognizing modification. Furthermore, LEF1 promoted upregulating c-Myc Cyclin D1 expression, as well participated mediating IGF2BP1-induced activity under unloading. Notably, Melatonin (MT) might participate IGF2BP1/LEF1 axis, thereby regulating Collectively, study revealed a new insight into MT/IGF2BP1/LEF1 pathway process unloading-induced loss, which potentially contribute establishing therapeutic strategies for osteoporosis.

Язык: Английский

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The biological roles and molecular mechanisms of m6A reader IGF2BP1 in the hallmarks of cancer

Genes & Diseases, Год журнала: 2025, Номер unknown, С. 101567 - 101567

Опубликована: Фев. 1, 2025

Язык: Английский

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Development of 3-Arylaminothiophenic-2-carboxylic Acid Derivatives as New FTO Inhibitors Showing Potent Antileukemia Activities

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер 289, С. 117444 - 117444

Опубликована: Фев. 25, 2025

Язык: Английский

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RNA Binding Proteins as Potential Therapeutic Targets in Colorectal Cancer

Cancers, Год журнала: 2024, Номер 16(20), С. 3502 - 3502

Опубликована: Окт. 16, 2024

RNA-binding proteins (RBPs) play critical roles in regulating post-transcriptional gene expression, managing processes such as mRNA splicing, stability, and translation. In normal intestine, RBPs maintain the tissue homeostasis, but when dysregulated, they can drive colorectal cancer (CRC) development progression. Understanding molecular mechanisms behind CRC is vital for developing novel therapeutic strategies, are emerging key players this area. This review highlights of several RBPs, including LIN28, IGF2BP1-3, Musashi, HuR, CELF1, CRC. These regulate oncogenes tumor suppressor genes by influencing stability While targeting poses challenges due to their complex interactions with mRNAs, recent advances drug discovery have identified small molecule inhibitors that disrupt these interactions. inhibitors, which target IGF2BPs, shown promising results preclinical studies. Their ability modulate RBP activity presents a new avenue treating conclusion, offer significant potential targets Although technical remain, ongoing research into selective, potent, bioavailable should lead more effective treatments improved outcomes

Язык: Английский

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Interactive Structural Analysis of KH3-4 Didomains of IGF2BPs with Preferred RNA Motif Having m6A Through Dynamics Simulation Studies

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(20), С. 11118 - 11118

Опубликована: Окт. 16, 2024

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Язык: Английский

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