A long non-coding RNA, APOA4-AS, regulates APOA4 expression depending on HuR in mice

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Long non-coding RNAs (lncRNAs) are increasingly recognized as crucial players in human diseases.
• Characterization of lncRNAs, particularly in metabolic disorders like fatty liver disease, remains limited.

Purpose of the Study:

• To identify novel lncRNAs associated with fatty liver disease.
• To elucidate the regulatory role of the identified lncRNA APOA4-AS in Apolipoprotein A-IV (APOA4) expression and its implications in fatty liver disease.

Main Methods:

• Bioinformatic screening and experimental validation of lncRNAs in fatty liver disease models.
• In vitro and in vivo knockdown experiments of APOA4-AS.
• Analysis of APOA4 expression, plasma lipid levels, and interaction with HuR protein.

Main Results:

• Fifteen lncRNAs associated with fatty liver disease were identified, including APOA4-AS.
• APOA4-AS expression is elevated in fatty liver conditions and positively correlates with APOA4 expression.
• Knockdown of APOA4-AS reduces APOA4 expression, plasma triglyceride, and total cholesterol in ob/ob mice.
• APOA4-AS stabilizes APOA4 mRNA through interaction with HuR, a process essential for maintaining both transcripts.

Conclusions:

• APOA4-AS is a novel anti-sense lncRNA that co-expresses with and specifically regulates APOA4 expression.
• The APOA4-AS/APOA4 axis, involving HuR, plays a significant role in the pathogenesis of fatty liver disease.
• APOA4-AS represents a potential diagnostic biomarker and therapeutic target for fatty liver disease.