Related Experiment Video

Updated: Sep 5, 2025

Author Spotlight: Deciphering the Role of ATM in Ataxia-Telangiectasia and the Associated Cerebellar Degeneration
08:41

Author Spotlight: Deciphering the Role of ATM in Ataxia-Telangiectasia and the Associated Cerebellar Degeneration

Published on: December 27, 2024

1.6K

A Novel ATM Antisense Transcript ATM-AS Positively Regulates ATM Expression in Normal and Breast Cancer Cells

He Cheng1,2, Er-Shao Zhang1, Xiao Shi1

  • 1Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, 210000, China.

Current Medical Science
|July 5, 2022
PubMed
Abstract

Insights

A novel antisense transcript, ATM-AS, upregulates the ataxia telangiectasia mutated (ATM) gene by recruiting KAT5. This ATM-AS regulation is crucial for DNA damage repair and impacts breast cancer prognosis.

Area of Science:

  • Molecular Biology
  • Cancer Genetics
  • Epigenetics

Background:

  • The ataxia telangiectasia mutated (ATM) gene is vital for DNA damage response and its dysregulation is common in breast cancer.
  • The precise mechanisms governing ATM expression in cancer remain incompletely understood.
  • Bioinformatic analysis predicted a novel antisense transcript, ATM-antisense (AS), originating from the ATM gene locus.

Purpose of the Study:

  • To identify and characterize the predicted ATM-AS transcript.
  • To investigate the regulatory role of ATM-AS in ATM gene expression.
  • To explore the functional significance of ATM-AS in breast cancer biology and patient prognosis.

Main Methods:

  • Verification of ATM-AS using single strand-specific RT-PCR.
  • Quantification of ATM-AS and ATM expression via qRT-PCR and Western blotting in cell lines and tissues.
  • Functional assays including luciferase reporter assays, mass spectrometry, ChIP-qPCR, and RIP to elucidate regulatory mechanisms.
  • Assessment of DNA damage repair via immunofluorescence and HCR assays.
  • Correlation analysis of ATM-AS levels with ATM expression and patient prognosis in breast cancer tissues.

Main Results:

  • ATM-AS was identified and found to be upregulated in breast cancer.
  • ATM-AS positively regulates ATM gene expression by recruiting KAT5 histone acetyltransferase to the ATM promoter.
  • Reduced ATM-AS levels impaired ATM-mediated DNA damage repair in vitro.
  • ATM-AS expression positively correlated with ATM expression and improved patient prognosis in breast cancer tissues.

Conclusions:

  • ATM-AS is a novel, essential positive regulator of ATM expression, functioning via KAT5 recruitment to the ATM promoter.
  • This study reveals a new mechanism for ATM gene dysregulation in breast cancer.
  • The findings enhance understanding of how antisense transcripts regulate their host genes and impact cancer outcomes.
Keywords:
KAT5antisense transcriptataxia telangiectasia mutatedataxia telangiectasia mutated-antisensebreast cancer

More Related Videos

Examining the Dynamics of Cellular Adhesion and Spreading of Epithelial Cells on Fibronectin During Oxidative Stress10:57

Examining the Dynamics of Cellular Adhesion and Spreading of Epithelial Cells on Fibronectin During Oxidative Stress

Published on: October 13, 2019

7.6K
Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies07:47

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies

Published on: September 15, 2023

1.6K

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.9K
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...
9.3K
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.9K
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
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.8K
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.8K