相关实验视频

Updated: Jan 10, 2026

Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells

Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells

Published on: February 21, 2018

在MLL-AF4白血病中,IGF2BP3重塑了microRNA向格局

Lyna E S Kabbani¹, Shruti Kapoor¹, Gunjan Sharma²

¹Department of Molecular, Cell and Developmental Biology and Center for Molecular Biology of RNA, University of California Santa Cruz, Santa Cruz, CA.

bioRxiv : the preprint server for biology

|November 24, 2025

概括

胰岛素样生长因子2 mRNA结合蛋白3 (IGF2BP3) 通过阻断RNA沉默来放大白血病. 它与RISC复合体竞争,防止瘤性mRNA的抑制,促进癌症生长.

科学领域:

分子生物学分子生物学
癌症生物学癌症生物学
在RNA生物学,RNA生物学.

背景情况:

胰岛素样生长因子2 mRNA结合蛋白3 (IGF2BP3) 对于MLL-AF4驱动的白血病发生至关重要.
IGF2BP3在放大致癌基因表达的机制尚未完全理解.

研究的目的:

研究IGF2BP3在调节RNA诱导沉默复合体 (RISC) 相互作用中的作用.
阐明IGF2BP3如何在B细胞急性淋巴细胞白血病 (B-ALL) 中放大瘤基因表达.

主要方法:

在IGF2BP3淘汰 (I3KO) 和控制B-ALL细胞系中进行了AGO2 miR-eCLIP.
分析的模拟miRNA-mRNA读取以评估差异性miRNA占用率.
进行生物化学测试以确认蛋白质相互作用.

主要成果:

在3'UTRs上确定了111个依赖IGF2BP3的AGO2结合位点.
在I3KO细胞中观察到miR-181a的向性增加,这表明IGF2BP3限制了miR-181a介导的抑制.
在IGF2BP3和AGO2-miRNA复合体之间进行3'-UTR结合的直接竞争得到证实.

结论:

通过对抗RISC介导的瘤性mRNAs的抑制,IGF2BP3促进白血病发生.
IGF2BP3通过与RISC复合体竞争,与目标3'UTR结合.
这种机制强调IGF2BP3作为MLL-AF4驱动型白血病的潜在治疗点.

更多相关视频

Investigation of Genetic Dependencies Using CRISPR-Cas9-based Competition Assays

Investigation of Genetic Dependencies Using CRISPR-Cas9-based Competition Assays

Published on: January 7, 2019

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

相关概念视频

MicroRNAs

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...

Chromatin Modification in iPS Cells

Chromatin Modification in iPS Cells

Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...