Related Experiment Video

Updated: Jul 2, 2026

CRISPR Gene Editing Tool for MicroRNA Cluster Network Analysis
10:40

CRISPR Gene Editing Tool for MicroRNA Cluster Network Analysis

Published on: April 25, 2022

c-Myb oncoprotein is an essential target of the dleu2 tumor suppressor microRNA cluster

Elaine Y Chung1, Michael Dews, Diana Cozma

  • 1Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Cancer Biology & Therapy
|August 19, 2008
PubMed

Insights

The dleu2 tumor suppressor locus, encoding miR-15a and miR-16 microRNAs, is downregulated by the Pax5 oncoprotein. These microRNAs target c-Myb, a key protein in B-cell neoplasms.

Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Regulation

Background:

  • The dleu2 tumor suppressor locus encodes miR-15a and miR-16, microRNAs implicated in B-cell neoplasms.
  • The regulatory network involving this microRNA cluster and associated proteins is not well understood.

Purpose of the Study:

  • To investigate the relationship between the Pax5 oncoprotein, the dleu2 microRNA cluster (miR-15a/16), and its downstream targets.
  • To elucidate the role of miR-15a/16 in regulating c-Myb expression and its impact on Pax5 function.

Main Methods:

  • Luciferase sensor assays to validate microRNA binding sites.
  • Overexpression studies of miR-15a/16 and c-Myb in relevant cellular models.
  • Analysis of endogenous protein and gene expression levels.

Main Results:

  • Pax5 oncoprotein was found to downregulate the dleu2 gene and upregulate its partner, c-Myb, post-transcriptionally.
  • miR-15a/16 were confirmed to bind to the c-Myb 3'-UTR, reducing protein output.
  • Overexpression of miR-15a/16 reduced endogenous c-Myb levels and impaired Pax5 function.
  • Restoration of c-Myb levels partially rescued the tumor suppressive effects of miR-15a/16.

Conclusions:

  • c-Myb is identified as a key downstream target of the miR-15a/16 microRNA cluster.
  • The interplay between Pax5, miR-15a/16, and c-Myb is crucial for regulating B-cell neoplasm development.
  • This study sheds light on a novel regulatory pathway in B-cell malignancies.

Related Concept Videos

MicroRNAs01:22

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...
MicroRNAs01:22

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 ends...
MicroRNAs01:22

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 ends...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...