Rubina Kseniya, Maier Artem, Klimovich Polina, Sysoeva Veronika, Romashin Daniil, Semina Ekaterina, Tkachuk Vsevolod
Faculty of Medicine, Lomonosov Moscow State University, 119991 Moscow, Russia.
Institute of Experimental Cardiology, National Medical Research Center of Cardiology Named After Academician E.I. Chazov, 121552 Moscow, Russia.
Int J Mol Sci. 2025 Jun 26;26(13):6127. doi: 10.3390/ijms26136127.
T-cadherin () 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 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 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 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- crosstalk between health and disease, opening new avenues for biomarker discovery and RNA-based therapeutics.
T-钙黏蛋白（）是一种非典型的、糖基磷脂酰肌醇锚定的钙黏蛋白，其功能范围从轴突导向和血管模式形成到脂肪因子信号传导和细胞命运决定。最初它被鉴定为迁移的神经嵴细胞、投射轴突和生长血管的同源信号，后来又成为心脏保护型高分子量脂联素和致动脉粥样硬化的低密度脂蛋白的双重代谢受体。我们最近发现，缺乏T-钙黏蛋白的间充质干/基质细胞易于发生脂肪生成，这突出了其在谱系选择中的作用。新出现的证据表明，其表达和功能受到非编码RNA（ncRNA）的精细调节。MiR-199b-5p、miR-377-3p、miR-23a/27a/24-2以及miR-142家族直接结合其3'-UTR或其表观遗传调节因子，影响转录或加速降解。长链非编码RNA（lncRNA），包括反义转录本CDH13-AS1/AS2、脑限制性的FEDORA以及上下文依赖性的LINC00707和UPAT，要么吸附这些miRNA，要么将DNMT/TET酶招募到其启动子区域。环状RNA（circRNA），即circCDH13和circ_0000119，可以通过隔离miRNA抑制因子或增强DNMT1来增加另一层复杂性。总的来说，这种ncRNA调控网络在心血管、代谢、致癌和神经退行性疾病中调节T-钙黏蛋白。本综述整合了实验验证数据和计算机预测结果，以描绘健康与疾病之间的ncRNA相互作用，为生物标志物发现和基于RNA的治疗开辟新途径。
