Differential expression pattern, bioinformatics analysis, and validation of circRNA and mRNA in patients with

Yunyun Liu1,2, Kangjie Wang3, Guanhua Li4

  • 1Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Insights

This study identifies novel circular RNAs (circRNAs) involved in arteriosclerosis obliterans (ASO). Knocking down circRNA-0008706 suppressed cell proliferation and migration, suggesting it as a potential therapeutic target for ASO.

Area of Science:

  • Vascular Biology
  • Molecular Biology
  • Genomics

Background:

  • Arteriosclerosis Obliterans (ASO) involves plaque buildup in lower limb arteries, leading to amputation and impacting patient health.
  • ASO incidence is rising, affecting younger populations, highlighting the need for better understanding.
  • Circular RNAs (circRNAs) are implicated in various diseases, but their role in ASO pathogenesis remains largely unexplored.

Purpose of the Study:

  • To investigate the differential expression of circRNAs and mRNAs in ASO arterial specimens.
  • To construct a competing endogenous (ceRNA) network specific to ASO.
  • To explore the functional role of a specific circRNA, circRNA-0008706, in ASO pathogenesis.

Main Methods:

  • Second-generation sequencing of arterial tissues from ASO patients and healthy donors.
  • Bioinformatic analysis to identify differentially expressed circRNAs and mRNAs and construct a ceRNA network.
  • Validation using PCR and agarose gel electrophoresis; functional analysis via siRNA-mediated knockdown of circRNA-0008706 in human arterial smooth muscle cells (HASMCs).

Main Results:

  • Identified 480 differentially expressed circRNAs and 2,997 differentially expressed mRNAs.
  • Enriched pathways included epithelial-to-mesenchymal transition (EMT) and lipid transport.
  • Knockdown of circRNA-0008706 inhibited HASMC proliferation and migration and reduced BCAT1 expression, potentially via interaction with microRNA-125b-5p.

Conclusions:

  • This study provides the first comprehensive comparison of circRNA and mRNA profiles in ASO.
  • A novel ASO-specific ceRNA network was constructed.
  • circRNA-0008706 emerges as a potential therapeutic target for ASO.
Abstract