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Regulation of PHOX2B gene expression by the long non-coding natural antisense RNA PHOX2B-AS1
Simona Di Lascio1, Ana Lucia Cuadros Gamboa1, Martina Bertocchi1
1Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy.
The FEBS Journal
|January 24, 2026
Summary
Paired mesoderm homeobox protein 2B (PHOX2B) is crucial for nervous system development and neuroblastoma. This study reveals a newly identified antisense transcript, PHOX2B-AS1, that is reciprocally regulated by PHOX2B.
Area of Science:
- Genetics
- Molecular Biology
- Neuroscience
Background:
- Paired mesoderm homeobox protein 2B (PHOX2B) is a key transcription factor in autonomic nervous system development.
- PHOX2B mutations are linked to neurodevelopmental disorders and neuroblastoma.
- Regulation of PHOX2B gene expression and its antisense strand remains largely uncharacterized.
Purpose of the Study:
- To characterize the human PHOX2B-AS1 and mouse Phox2b antisense transcripts.
- To investigate the regulatory relationship between PHOX2B and its antisense transcript.
Main Methods:
- Bioinformatics analysis to identify antisense transcripts.
- Experimental validation of PHOX2B-AS1 and mouse Phox2b.
- Functional studies to assess the impact of antisense transcript inhibition on PHOX2B levels.
Main Results:
- The human PHOX2B-AS1 and mouse Phox2b antisense transcripts were identified and characterized.
- PHOX2B was found to positively regulate PHOX2B-AS1 expression.
- Inhibition of PHOX2B-AS1 led to a decrease in PHOX2B protein levels.
Conclusions:
- Evidence supports the existence of a functional antisense gene to PHOX2B.
- A strict correlation and reciprocal regulation exists between PHOX2B and PHOX2B-AS1.
- This interaction offers new insights into PHOX2B gene regulation relevant to neurodevelopmental disorders and neuroblastoma.
Keywords:
PHOX2Bcongenital central hypoventilation syndromelncRNAnatural antisense transcriptneuroblastomaMore Related Videos
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