circRNA_013145-miR-185-5p-RhoA axis: A novel mechanism in the pathophysiology of diabetes-induced erectile dysfunction

METTL3-mediated N6-methyladenosine modification of circHUWE1 promotes high glucose-induced cardiomyocyte apoptosis and ferroptosis-related alterations through regulating miR-671-5p/CELF1 axis

Circular RNA circPSEN1 promotes neovascularization by regulating the miR-150-5p/TRIM65 axis in diabetic retinopathy

Mechanistically, circPSEN1 acts as a sponge for miR-150-5p, enhancing TRIM65 expression and contributing to DR pathogenesis, indicating that circPSEN1 may serve as a therapeutic target for DR.

Circulating Circ_0089762 Predicts Adverse Outcomes in Acute Myocardial Infarction Via Regulating miR‑938/STAT3‑Mediated Endothelial Dysfunction.

The cardiac protective human circular RNA circKLHL20_009 sponges miR-31-5p to ameliorate myocardial hypertrophy and fibrosis through suppressing β-catenin signaling.

CircRNA hsa_circ_0001946 promotes hypertrophic scar pathogenesis via the miR-514a-3p/COL5A2 axis.

Hypertrophic scars (HSs) represent a fibroproliferative disorder characterized by excessive extracellular matrix deposition. However, the underlying regulatory mechanisms involving circular RNAs (circRNAs) have not yet been fully elucidated. This study aimed to delineate the circRNA expression landscape in HS and reveal the functional roles of a specific candidate circRNA through the competing endogenous RNA (ceRNA) network. Eighty-one differentially expressed circRNAs (DEcircRNAs) were identified in five paired HS and normal skin samples by high-throughput sequencing. Functional enrichment analysis of host genes highlighted pathways involving cell proliferation and ECM-receptor interactions. CircRNA-miRNA-mRNA network analysis revealed hsa_circ_0001946 as a significantly upregulated candidate circRNA. Subsequent RT-qPCR validated its elevation in human HS tissues and hypertrophic scar fibroblasts (HSFs). Subcellular fractionation and RNase R assays confirmed its cytoplasmic localization and circular stability. Functionally, knockdown of hsa_circ_0001946 significantly inhibited HSF proliferation, migration, and collagen gel contraction. Mechanistically, dual-luciferase reporter assays demonstrated that hsa_circ_0001946 acts as a sponge for miR-514a-3p; notably, silencing hsa_circ_0001946 attenuated the pro-fibrotic effects induced by miR-514a-3p inhibition. Furthermore, miR-514a-3p was shown to directly target and suppress COL5A2. Collectively, these findings establish that hsa_circ_0001946 promotes HS development by sequestering miR-514a-3p to derepress COL5A2 expression. This study identifies the hsa_circ_0001946/miR-514a-3p/COL5A2 axis as a novel pathogenic mechanism contributing to HS formation, suggesting hsa_circ_0001946 as a promising intervention target for mitigating pathological scarring.

A potential role of the circ_UBR4/miR-10a-5p/KLF4 axis in regulating vascular smooth muscle cell phenotypic transformation : implications for cardiac allograft vasculopathy.

Cardiac Allograft Vasculopathy (CAV) remains a predominant challenge in post-transplant cardiac care. The phenotypic transformation of vascular smooth muscle cells (VSMCs) is central to its progression, contributing to neointimal hyperplasia and long-term graft failure. Recent studies have highlighted the involvement of non-coding RNAs as essential modulators in VSMC regulation, opening new avenues for therapeutic exploration. In this study, we aimed to explore the role of the circ_UBR4/miR-10a-5p/KLF4 regulatory axis in VSMC phenotypic switching. Human aortic smooth muscle cells (HASMCs) underwent co-transfection with constructed plasmids of both wild-type and mutated sequences for circ_UBR4 and KLF4, along with respective miR-10a-5p mimics or controls. Functional and mechanistic assays, including dual-luciferase reporter analysis, flow cytometry, Transwell migration and invasion assays, qRT-PCR, Western blotting, and immunofluorescence, were utilized to investigate interactions and downstream effects. Our results revealed that circ_UBR4 directly interacts with miR-10a-5p, and its suppression led to attenuated VSMC proliferation and migration. This inhibitory effect was reversed by concurrent miR-10a-5p downregulation, suggesting a functional antagonism. Further analyses demonstrated that miR-10a-5p directly targets KLF4, and its overexpression resulted in decreased proliferative capacity and reduced expression of synthetic and proliferative markers (e.g., OPN, MMP-2, PCNA, and ki-67). These effects were counteracted by KLF4 overexpression. In parallel, contractile marker SM-22α showed opposing trends, further confirming phenotypic transition. Together, these findings suggest that the circ_UBR4/miR-10a-5p/KLF4 axis may play a critical role in regulating VSMC phenotypic plasticity. Insights from this study provide new molecular insights that could inform our understanding of CAV pathogenesis and may represent potential targets for future therapeutic exploration in transplant cardiology.