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ATG10 antisense RNA 1 (ATG10-AS1)
- Target
- ATG10-AS1
- Molecular classification
- Long noncoding RNA (lncRNA), Regulatory RNA
01
Overview
ATG10 antisense RNA 1 (ATG10-AS1) is a long noncoding RNA that acts as a regulator of autophagy by modulating the expression of its sense gene, ATG10. It operates by associating with the protein ELAVL1 and promoting activating histone modifications at the ATG10 promoter, thereby enhancing ATG10 transcription. Elevated levels of ATG10-AS1, especially within exosomes, are linked to increased resistance of breast cancer cells to trastuzumab through activation of autophagy pathways, marking it as a promising therapeutic target and a potential biomarker for predicting treatment effectiveness. ATG10-AS1 does not encode a protein and is classified as a regulatory RNA, with primary relevance in oncology. There are currently no approved drugs that directly target ATG10-AS1, but antisense oligonucleotides targeting ATG10-AS1 have shown preclinical efficacy at overcoming drug resistance.
- Other names
- ATG10-AS1ATG10 antisense RNA 1
02
Mechanism of action
Epigenetic activation of ATG10 transcription via recruitment of ELAVL1 and modification of histone marks (H3K27ac, H3K4me3); Regulation of autophagy pathways leading to increased drug resistance; Antisense oligonucleotide-mediated knockdown reverses resistance to trastuzumab
03
Biological functions
Regulation of autophagyEpigenetic regulation of gene expressionModulation of drug resistance (notably trastuzumab resistance in HER-2-positive breast cancer)Intercellular communication via exosomes
04
Disease associations
Cancer (especially breast cancer and resistance to HER2-targeted therapies)Potential roles in other malignancies by regulating autophagic activity
05
Safety considerations
Therapeutic targeting may affect global autophagy, with potential for undesirable effects on normal cellular homeostasis and immune responseIncomplete understanding of off-target or systemic effects due to RNA-based therapies and modulation of autophagy
06
Interacting drugs
1 more in the full profile.
07
Biomarkers
Serum/exosomal ATG10-AS1 levels are predictive of poor response to trastuzumab in HER2-positive breast cancer
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