Molecule Information

General Information of the Molecule (ID: Mol04175)

Name	Deiodinase, iodothyronine type III, opposite strand (DIO3OS) ,Homo sapiens
Synonyms	DIO3OS Click to Show/Hide
Molecule Type	LncRNA
Gene Name	DIO3OS
Gene ID	64150
Ensembl ID	ENSG00000258498
*Click to Show/Hide the Complete Species Lineage*
Kingdom: Metazoa Phylum: Chordata Class: Mammalia Order: Primates Family: Hominidae Genus: Homo Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s)

2 drug(s) in total

Click to Show/Hide the Full List of Drugs

Anastrozole

Click to Show/Hide

Drug Resistance Data Categorized by Their Corresponding Mechanisms
Metabolic Reprogramming via Altered Pathways (MRAP)		Click to Show/Hide
Disease Class: Breast adenocarcinoma [ICD-11: 2C60.1]			[1]
Metabolic Type	Glucose metabolism
Resistant Disease	Breast adenocarcinoma [ICD-11: 2C60.1]		Disease Info
Resistant Drug	Anastrozole		Drug Info
Molecule Alteration	Expression	Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
In Vivo Model	Four-week-old female athymic BALB/c nude mice, with tumor cells		Mice
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Tumor volume assay
Mechanism Description	Mechanistically, DIO3OS interacts with polypyrimidine tract binding protein 1 (PTBP1) and stabilizes the mRNA of lactate dehydrogenase A (LDHA) by protecting the integrity of its 3'UTR, and subsequently upregulates LDHA expression and activates glycolytic metabolism in AI-resistant breast cancer cells. Our findings highlight the role of lncRNA in regulating the key enzyme of glycolytic metabolism in response to endocrine therapies and the potential of targeting DIO3OS to reverse AI resistance in ER-positive breast cancer.

Letrozole

Click to Show/Hide

Drug Resistance Data Categorized by Their Corresponding Mechanisms
Metabolic Reprogramming via Altered Pathways (MRAP)		Click to Show/Hide
Disease Class: Breast adenocarcinoma [ICD-11: 2C60.1]			[1]
Metabolic Type	Glucose metabolism
Resistant Disease	Breast adenocarcinoma [ICD-11: 2C60.1]		Disease Info
Resistant Drug	Letrozole		Drug Info
Molecule Alteration	Expression	Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
In Vivo Model	Four-week-old female athymic BALB/c nude mice, with tumor cells		Mice
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Tumor volume assay
Mechanism Description	Mechanistically, DIO3OS interacts with polypyrimidine tract binding protein 1 (PTBP1) and stabilizes the mRNA of lactate dehydrogenase A (LDHA) by protecting the integrity of its 3'UTR, and subsequently upregulates LDHA expression and activates glycolytic metabolism in AI-resistant breast cancer cells. Our findings highlight the role of lncRNA in regulating the key enzyme of glycolytic metabolism in response to endocrine therapies and the potential of targeting DIO3OS to reverse AI resistance in ER-positive breast cancer.

References

Ref 1	Long noncoding RNA DIO3OS induces glycolytic-dominant metabolic reprogramming to promote aromatase inhibitor resistance in breast cancer. Nat Commun. 2022 Nov 22;13(1):7160.