Related Experiment Video

Updated: Sep 23, 2025

Clinicopathological Analysis of miRNA Expression in Breast Cancer Tissues by Using miRNA In Situ Hybridization
06:01

Clinicopathological Analysis of miRNA Expression in Breast Cancer Tissues by Using miRNA In Situ Hybridization

Published on: June 7, 2016

6.9K

MicroRNA-449a Inhibits Triple Negative Breast Cancer by Disturbing DNA Repair and Chromatid Separation

Beate Vajen1, Rahul Bhowmick2, Luisa Greiwe1

  • 1Department of Human Genetics, Hannover Medical School, Carl-Neuberg-Str. 1, 30629 Hannover, Germany.

International Journal of Molecular Sciences
|May 14, 2022
PubMed

Insights

MicroRNA-449a induces apoptosis in triple-negative breast cancer (TNBC) by increasing chromosomal instability (CIN). This microRNA targets EME1 and inhibits DNA repair, offering a new therapeutic strategy for TNBC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Chromosomal instability (CIN) drives tumorigenesis and is a therapeutic target in triple-negative breast cancer (TNBC).
  • Poly(ADP-ribose) polymerase inhibitors (PARPi) increase CIN in DNA repair-deficient TNBC cells, leading to apoptosis.

Purpose of the Study:

  • To investigate the role of microRNA-449a in chromosomal instability (CIN) and its therapeutic potential in triple-negative breast cancer (TNBC).

Main Methods:

  • Transfection of TNBC cell lines with microRNA-449a mimics.
  • Microarray analysis to assess gene expression changes.
  • Immunoprecipitation and luciferase assays to identify target genes.
  • Analysis of chromosomal aberrations (ultrafine bridges, 53BP1 foci, micronuclei).

Main Results:

  • MicroRNA-449a mimics induced apoptosis, reduced proliferation, and decreased homology-directed repair (HDR) gene expression in TNBC cells.
  • EME1 was identified as a direct target of microRNA-449a, and its downregulation increased chromosomal instability.
  • MicroRNA-449a induced apoptosis via chromatid mis-segregation (targeting EME1) and HDR inhibition (downregulating E2F3, BIRC5, BRCA2, RAD51).
  • Ectopic microRNA-449a expression enhanced PARPi toxicity in cells with BRCA1 variants.

Conclusions:

  • MicroRNA-449a plays a novel role in inducing chromosomal instability (CIN) and apoptosis in triple-negative breast cancer (TNBC).
  • MicroRNA-449a represents a potential therapeutic target for TNBC, particularly in combination with PARPi therapy for BRCA1-mutated cancers.
Keywords:
DNA repairchromatid separationchromosomal instabilitymicroRNA449atriple negative breast cancer

More Related Videos

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library08:40

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library

Published on: April 6, 2012

17.7K
CRISPR Gene Editing Tool for MicroRNA Cluster Network Analysis10:40

CRISPR Gene Editing Tool for MicroRNA Cluster Network Analysis

Published on: April 25, 2022

2.5K

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...
3.1K
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.1K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.4K
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.1K
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...
4.6K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
36.2K