MicroRNA-125b transforms myeloid cell lines by repressing multiple mRNA.
Marina Bousquet1, Diu Nguyen, Cynthia Chen
1Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, Nine Cambridge Center, Cambridge, MA 02142, USA. bousquetmarina@gmail.com
Haematologica
|June 13, 2012
Summary
MicroRNA miR-125b acts as an oncomiR, transforming myeloid cells by blocking differentiation and apoptosis. This microRNA targets CBFB and genes in the p53 pathway, promoting leukemia development.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- A chromosomal translocation t(2;11)(p21;q23) leads to miR-125b overexpression in myeloid malignancies.
- Previous studies showed miR-125b overexpression induces leukemia in mice.
Purpose of the Study:
- Investigate the mechanism of myeloid transformation driven by miR-125b.
- Identify novel targets of miR-125b in myeloid cells.
Main Methods:
- Utilized human (NB4, HL60) and murine (32Dclone3) promyelocytic cell lines.
- Performed xenograft experiments in nude mice to assess transformation.
- Employed RNA-sequencing to compare transcriptomes of miR-125b overexpressing and control cell lines.
Main Results:
- miR-125b overexpression inhibited apoptosis and myeloid differentiation while enhancing proliferation.
- Transformed 32Dclone3 cells exhibited interleukin-3 independent growth and formed tumors in vivo.
- Identified ABTB1 and CBFB as direct targets of miR-125b.
- Demonstrated miR-125b downregulates p53 pathway genes (BAK1, TP53INP1), affecting apoptosis.
Conclusions:
- miR-125b functions as an oncomiR in myeloid cells, promoting transformation.
- Targeting CBFB disrupts myeloid differentiation, while p53 pathway inhibition affects apoptosis.
- ABTB1 downregulation by miR-125b contributes to the proliferative advantage in myeloid leukemia.
Related Concept Videos
01:22MicroRNAs
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...
01:22MicroRNAs
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 ends...
01:22MicroRNAs
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 ends...
02:15Experimental RNAi
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
01:23Types of RNA
Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...