Related Experiment Video

Updated: Dec 13, 2025

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

7.5K

lncRNA ZNF649-AS1 Induces Trastuzumab Resistance by Promoting ATG5 Expression and Autophagy

Mingli Han1, Xueke Qian1, Hui Cao2

  • 1Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

Molecular Therapy : the Journal of the American Society of Gene Therapy
|August 1, 2020
PubMed

Insights

Long non-coding RNA ZNF649-AS1 promotes trastuzumab resistance in breast cancer by increasing autophagy. Its upregulation, driven by H3K27ac modification, involves PTBP1 to boost ATG5 transcription, worsening patient outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • The role of long non-coding RNAs (lncRNAs) in trastuzumab resistance remains unclear.
  • Understanding lncRNA regulation is crucial for improving breast cancer treatment efficacy.

Purpose of the Study:

  • To identify and investigate the function of dysregulated lncRNAs in trastuzumab resistance.
  • To elucidate the regulatory mechanism of ZNF649-AS1 in breast cancer.

Main Methods:

  • Differential expression analysis using HiSeq sequencing and qRT-PCR.
  • Interaction studies via mass spectrometry, RNA-FISH, and immunoprecipitation.
  • Assessment of ZNF649-AS1 knockdown effects on trastuzumab resistance and autophagy.

Main Results:

  • ZNF649-AS1 expression is elevated in trastuzumab-resistant cells and linked to poorer patient survival.
  • H3K27ac modification upregulates ZNF649-AS1 during trastuzumab treatment.
  • ZNF649-AS1 knockdown reverses resistance by modulating ATG5 and autophagy.

Conclusions:

  • H3K27ac-induced ZNF649-AS1 upregulation contributes to trastuzumab resistance.
  • ZNF649-AS1 interacts with PTBP1 to promote ATG5 transcription, enhancing autophagy.
  • ZNF649-AS1 represents a potential therapeutic target for overcoming trastuzumab resistance.
Keywords:
ATG5ZNF649-AS1autophagybreast cancertrastuzumab resistance

More Related Videos

High-Content Screening Assay for the Identification of Antibody-Dependent Cellular Cytotoxicity Modifying Compounds13:59

High-Content Screening Assay for the Identification of Antibody-Dependent Cellular Cytotoxicity Modifying Compounds

Published on: August 18, 2023

2.6K

Related Concept Videos

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...
9.6K
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

3.2K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.6K
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...
4.5K