Circular RNA RBM33 contributes to extracellular matrix degradation via miR-4268/EPHB2 axis in abdominal aortic aneurysm

Shizhi Wang; Qingwen Yuan; Wenpeng Zhao; Weimin Zhou

doi:10.7717/peerj.12232

Circular RNA RBM33 contributes to extracellular matrix degradation via miR-4268/EPHB2 axis in abdominal aortic aneurysm

PeerJ. 2021 Nov 16:9:e12232. doi: 10.7717/peerj.12232. eCollection 2021.

Authors

Shizhi Wang¹, Qingwen Yuan¹, Wenpeng Zhao¹, Weimin Zhou¹

Affiliation

¹ Department of Vascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Abstract

Background: Abdominal aortic aneurysm (AAA) is a complex vascular disease involving expansion of the abdominal aorta. Extracellular matrix (ECM) degradation is crucial to AAA pathogenesis, however, the specific molecular mechanism remains unclear. This study aimed to investigate differentially expressed circular RNAs (DEcircRNAs) involved in ECM degradation of AAA.

Methods: Transcriptome sequencing was used to analyze the DEcircRNAs between the AAA tissues and normal tissues. The expression of circRNAs in tissues and cells was validated using quantitative reverse transcription PCR (RT-qPCR). Overexpression of circRNAs in vascular smooth muscle cells (VSMCs) treated with angiotensin II (Ang II) was employed to explore its effect on ECM degradation of AAA. Bioinformatic technology, luciferase reporter gene assay, RT-qPCR, and rescue experiment were employed to evaluate the regulatory mechanism of circRNA.

Results: We identified 65 DEcircRNAs in AAA tissues compared with normal abdominal aortic tissues, including 30 up-regulated and 35 down-regulated circRNAs, which were mainly involved in inflammation and ECM-related functions and pathways. Moreover, circRBM33 was significantly increased in AAA tissues and Ang II-induced VSMCs compared with control samples. Overexpression of circRBM33 increased the expression of ECM-related molecule matrix metalloproteinase-2 and reduced the tissue inhibitor of matrix metalloproteinases-1 expression. Mechanistically, miR-4268 targeted binding to circRBM33 and inhibited the luciferase activity of circRBM33. Overexpression of circRBM33 induced the expression of EPH receptor B2 (EPHB2), and this effect was countered by miR-4268 mimics.

Conclusions: Overall, our data suggest that circRBM33 might be involved in AAA progression by regulating ECM degradation via the miR-4268/EPHB2 axis.

Keywords: Abdominal aortic aneurysm; Circular RNAs; EPH receptor B2; Extracellular matrix degradation; Matrix metalloproteinase-2; Tissue inhibitor of matrix metalloproteinases-1; circRBM33.

Associated data

figshare/10.6084/m9.figshare.16441944.v3

Grants and funding

This work was supported by the Science and Technology Project of the Education Department of Jiangxi province (GJJ200197). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.