T-Cadherin (CDH13) and Non-Coding RNAs: The Crosstalk Between Health and Disease

Abstract

T-cadherin (CDH13) is an atypical, glycosyl-phosphatidylinositol-anchored cadherin with functions ranging from axon guidance and vascular patterning to adipokine signaling and cell-fate specification. Originally identified as a homophilic cue for migrating neural crest cells, projecting axons, and growing blood vessels, it later emerged as a dual metabolic receptor for cardioprotective high-molecular-weight adiponectin and atherogenic low-density lipoproteins. We recently showed that mesenchymal stem/stromal cells lacking T-cadherin are predisposed to adipogenesis, underscoring its role in lineage choice. Emerging evidence indicates that CDH13 expression and function are fine-tuned by non-coding RNAs (ncRNAs). MiR-199b-5p, miR-377-3p, miR-23a/27a/24-2, and the miR-142 family directly bind CDH13 3'-UTR or its epigenetic regulators, affecting transcription or accelerating decay. Long non-coding RNAs (lncRNAs), including antisense transcripts CDH13-AS1/AS2, brain-restricted FEDORA, and context-dependent LINC00707 and UPAT, either sponge these miRNAs or recruit DNMT/TET enzymes to the CDH13 promoter. Circular RNAs (circRNAs), i.e.circCDH13 and circ_0000119, can add a third level of complexity by sequestering miRNA repressors or boosting DNMT1. Collectively, this ncRNA circuitry regulates T-cadherin across cardiovascular, metabolic, oncogenic, and neurodegenerative conditions. This review integrates both experimentally validated data and in silico predictions to map the ncRNA-CDH13 crosstalk between health and disease, opening new avenues for biomarker discovery and RNA-based therapeutics.

Keywords: CDH13; T-cadherin; miRNA; non-coding RNA; regulation.

Figure 2

Several miRNAs directly bind the CDH13 3′-UTR and repress T-cadherin synthesis, notably miR-377-3p, miR-675, miR-199b-5p, and the let-7 family [76,87,99]. The miR-23a/27a/24-2 cluster silences CDH13 through an indirect route: it suppresses the demethylase TET1, while elevating the methyl-transferase DNMT3B, shifting the balance toward promoter hypermethylation and transcriptional repression [119]. Beyond miRNAs, circRNA circ_0000119 and lncRNA UPAT also converge on DNMT1/3-dependent methylation, reinforcing CDH13 repression [121,122]. Conversely, T-cadherin can influence the non-coding landscape itself: for example, it can lower miR-101-3p, thereby lifting inhibition of the cholesterol transporter ABCA1 [124]. Together, these layers of direct binding and epigenetic crosstalk intertwine CDH13 into a dynamic ncRNA network that fine-tunes its expression in embryogenesis and disease.

Figure 1

Genomic regions and transcripts of CDH13 indexed in the NCBI Gene ID database https://www.ncbi.nlm.nih.gov/gene/1012#top (accessed on 26 May 2025). Gray arrows within introns mark splice direction. Gene transcripts are shown in green, whereas non-coding RNA loci appear in purple; those highlighted in red are the specific ncRNAs discussed in this review. A complete graphical key is available in the NCBI legend (https://www.ncbi.nlm.nih.gov/tools/sviewer/legends/) (accessed on 26 May 2025).