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Published on: September 28, 2015
CircCBFB-mediated miR-28-5p facilitates abdominal aortic aneurysm via LYPD3 and GRIA4
Jianing Yue1, Ting Zhu1, Jue Yang1
1Department of Vascular Surgery, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Xuhui District, Shanghai 200032, China.
Heading Aims:
Abdominal aortic aneurysm (AAA) is featured by the growth impediment and apoptosis surge of VSMCs (vascular smooth muscle cells). MicroRNAs (miRNAs) are suggested to affect cellular behaviors including cell growth and apoptosis. This study concentrated on unraveling the emerging role of miR-28-5p in abdominal aortic aneurysm.
Materials And Methods:
Previously, miR-28-5p was reported to be highly expressed in AAA. Functional assays were utilized to determine the role of miR-28-5p in VSMC apoptosis. To narrow down the downstream mRNAs, bioinformatics methods were utilized. The interaction between miR-28-5p and GRIA4 (glutamate ionotropic receptor AMPA type subunit 4) or LYPD3 (LY6/PLAUR domain containing 3) was explored. Candidate circRNAs (circular RNAs) of miR-28-5p were identified. Rescue analyses validated function of circCBFB (core-binding factor subunit beta)/miR-28-5p/GRIA4/LYPD3 axis in VSMC apoptosis and growth.
Key Findings:
MiR-28-5p acted as an apoptosis driver while circCBFB, GRIA4 and LYPD3 exerted anti-apoptosis effects in VSMCs. Mechanically, GRIA4 and LYPD3 were suppressed by miR-28-5p. Moreover, circCBFB served as a sponge of miR-28-5p, releasing GRIA4 and LYPD3 from miR-28-5p suppression. Functionally, GRIA4, LYPD3 and miR-28-5p were required in circCBFB-mediated VSMC apoptosis.
Significance:
This work unveiled an innovative axis of circCBFB/miR-28-5p/GRIA4/LYPD3 in VSMC apoptosis, exerting its potential in providing new thoughts in AAA management.
Insights
This study reveals that the circCBFB/miR-28-5p/GRIA4/LYPD3 axis significantly impacts vascular smooth muscle cell apoptosis, offering new insights for abdominal aortic aneurysm management.
Area of Science:
- Molecular Biology
- Cell Biology
- Vascular Biology
Background:
- Abdominal aortic aneurysm (AAA) is characterized by vascular smooth muscle cell (VSMC) growth impairment and apoptosis.
- MicroRNAs (miRNAs) play a crucial role in regulating cellular processes like growth and apoptosis.
- miR-28-5p has been implicated in AAA pathogenesis.
Purpose of the Study:
- To investigate the role of miR-28-5p in VSMC apoptosis within the context of AAA.
- To identify downstream targets and regulatory mechanisms of miR-28-5p in AAA.
Main Methods:
- Functional assays to assess VSMC apoptosis.
- Bioinformatic analyses to identify downstream mRNA targets of miR-28-5p.
- Investigation of interactions between miR-28-5p, GRIA4, LYPD3, and circCBFB.
- Rescue experiments to validate the identified molecular axis.
Main Results:
- miR-28-5p promotes VSMC apoptosis, while circCBFB, GRIA4, and LYPD3 exhibit anti-apoptotic effects.
- miR-28-5p directly suppresses GRIA4 and LYPD3 expression.
- circCBFB acts as a molecular sponge for miR-28-5p, thereby releasing GRIA4 and LYPD3.
- The circCBFB/miR-28-5p/GRIA4/LYPD3 axis is essential for regulating VSMC apoptosis.
Conclusions:
- A novel circCBFB/miR-28-5p/GRIA4/LYPD3 axis regulating VSMC apoptosis has been elucidated.
- This axis presents a potential therapeutic target for managing abdominal aortic aneurysm.
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