T-Cadherin (CDH13) and Non-Coding RNAs: The Crosstalk Between Health and Disease
Abstract
1. Introduction
2. T-Cadherin/CDH13 Expression Landscapes in Development, Adult Tissues, and Disease
3. Non-Coding RNAs: A General Overview
4. Non-Coding RNAs Expressed from the CDH13 Gene
5. Regulation of CDH13/T-Cadherin Expression via Non-Coding RNAs
6. Non-Coding RNAs That Indirectly Regulate CDH13
7. Bioinformatically Predicted Non-Coding RNAs Regulating CDH13/T-Cadherin
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Acknowledgments
Conflicts of Interest
References
- Lee, S.W. H–Cadherin, a Novel Cadherin with Growth Inhibitory Functions and Diminished Expression in Human Breast Cancer. Nat. Med. 1996, 2, 776–782. [Google Scholar] [CrossRef] [PubMed]
- Kremmidiotis, G.; Baker, E.; Crawford, J.; Eyre, H.J.; Nahmias, J.; Callen, D.F. Localization of Human Cadherin Genes to Chromosome Regions Exhibiting Cancer-Related Loss of Heterozygosity. Genomics 1998, 49, 467–471. [Google Scholar] [CrossRef]
- Philippova, M.; Joshi, M.B.; Kyriakakis, E.; Pfaff, D.; Erne, P.; Resink, T.J. A Guide and Guard: The Many Faces of T-Cadherin. Cell. Signal. 2009, 21, 1035–1044. [Google Scholar] [CrossRef]
- Ranscht, B.; Bronner-Fraser, M. T-Cadherin Expression Alternates with Migrating Neural Crest Cells in the Trunk of the Avian Embryo. Development 1991, 111, 15–22. [Google Scholar] [CrossRef] [PubMed]
- George, S.J.; Beeching, C.A. Cadherin:Catenin Complex: A Novel Regulator of Vascular Smooth Muscle Cell Behaviour. Atherosclerosis 2006, 188, 1–11. [Google Scholar] [CrossRef]
- Hulpiau, P.; van Roy, F. Molecular Evolution of the Cadherin Superfamily. Int. J. Biochem. Cell Biol. 2009, 41, 349–369. [Google Scholar] [CrossRef]
- Rubina, K.A.; Semina, E.V.; Kalinina, N.I.; Sysoeva, V.Y.; Balatskiy, A.V.; Tkachuk, V.A. Revisiting the Multiple Roles of T-Cadherin in Health and Disease. Eur. J. Cell Biol. 2021, 100, 151183. [Google Scholar] [CrossRef] [PubMed]
- Philippova, M.; Ivanov, D.; Joshi, M.B.; Kyriakakis, E.; Rupp, K.; Afonyushkin, T.; Bochkov, V.; Erne, P.; Resink, T.J. Identification of Proteins Associating with Glycosylphosphatidylinositol- Anchored T-Cadherin on the Surface of Vascular Endothelial Cells: Role for Grp78/BiP in T-Cadherin-Dependent Cell Survival. Mol. Cell Biol. 2008, 28, 4004–4017. [Google Scholar] [CrossRef]
- Philippova, M.; Joshi, M.B.; Pfaff, D.; Kyriakakis, E.; Maslova, K.; Erne, P.; Resink, T.J. T-Cadherin Attenuates Insulin-Dependent Signalling, eNOS Activation, and Angiogenesis in Vascular Endothelial Cells. Cardiovasc. Res. 2012, 93, 498–507. [Google Scholar] [CrossRef]
- Joshi, M.B.; Philippova, M.; Ivanov, D.; Allenspach, R.; Erne, P.; Resink, T.J. T-Cadherin Protects Endothelial Cells from Oxidative Stress-Induced Apoptosis. FASEB J. 2005, 19, 1737–1739. [Google Scholar] [CrossRef]
- Hug, C.; Wang, J.; Ahmad, N.S.; Bogan, J.S.; Tsao, T.-S.; Lodish, H.F. T-Cadherin Is a Receptor for Hexameric and High-Molecular-Weight Forms of Acrp30/Adiponectin. Proc. Natl. Acad. Sci. USA 2004, 101, 10308–10313. [Google Scholar] [CrossRef] [PubMed]
- Denzel, M.S.; Scimia, M.-C.; Zumstein, P.M.; Walsh, K.; Ruiz-Lozano, P.; Ranscht, B. T-Cadherin Is Critical for Adiponectin-Mediated Cardioprotection in Mice. J. Clin. Investig. 2010, 120, 4342–4352. [Google Scholar] [CrossRef] [PubMed]
- Okamoto, Y.; Kihara, S.; Ouchi, N.; Nishida, M.; Arita, Y.; Kumada, M.; Ohashi, K.; Sakai, N.; Shimomura, I.; Kobayashi, H.; et al. Adiponectin Reduces Atherosclerosis in Apolipoprotein E-Deficient Mice. Circulation 2002, 106, 2767–2770. [Google Scholar] [CrossRef] [PubMed]
- Tanaka, Y.; Kita, S.; Nishizawa, H.; Fukuda, S.; Fujishima, Y.; Obata, Y.; Nagao, H.; Masuda, S.; Nakamura, Y.; Shimizu, Y.; et al. Adiponectin Promotes Muscle Regeneration through Binding to T-Cadherin. Sci. Rep. 2019, 9, 16. [Google Scholar] [CrossRef]
- Obata, Y.; Kita, S.; Koyama, Y.; Fukuda, S.; Takeda, H.; Takahashi, M.; Fujishima, Y.; Nagao, H.; Masuda, S.; Tanaka, Y.; et al. Adiponectin/T-Cadherin System Enhances Exosome Biogenesis and Decreases Cellular Ceramides by Exosomal Release. JCI Insight 2018, 3, e99680. [Google Scholar] [CrossRef]
- Rubina и др. T-Cadherin: A Missing Puzzle Between Cancer and Obesity. Available online: https://juniperpublishers.com/ijcsmb/IJCSMB.MS.ID.555726.php (accessed on 23 June 2025).
- Sysoeva, V.; Semina, E.; Klimovich, P.; Kulebyakin, K.; Dzreyan, V.; Sotskaya, E.; Shchipova, A.; Popov, V.; Shilova, A.; Brodsky, I.; et al. T-Cadherin Modulates Adipogenic Differentiation in Mesenchymal Stem Cells: Insights into Ligand Interactions. Front. Cell Dev. Biol. 2024, 12, 1446363. [Google Scholar] [CrossRef]
- Andreeva, A.V.; Kutuzov, M.A. Cadherin 13 in Cancer. Genes Chromosomes Cancer 2010, 49, 775–790. [Google Scholar] [CrossRef]
- Rubina, K.A.; Smutova, V.A.; Semenova, M.L.; Poliakov, A.A.; Gerety, S.; Wilkinson, D.; Surkova, E.I.; Semina, E.V.; Sysoeva, V.Y.; Tkachuk, V.A. Detection of T-Cadherin Expression in Mouse Embryos. Acta Naturae 2015, 7, 87–94. [Google Scholar] [CrossRef]
- Takeuchi, T.; Misaki, A.; Liang, S.B.; Tachibana, A.; Hayashi, N.; Sonobe, H.; Ohtsuki, Y. Expression of T-Cadherin (CDH13, H-Cadherin) in Human Brain and Its Characteristics as a Negative Growth Regulator of Epidermal Growth Factor in Neuroblastoma Cells. J. Neurochem. 2000, 74, 1489–1497. [Google Scholar] [CrossRef]
- Ivanov, D.; Philippova, M.; Antropova, J.; Gubaeva, F.; Iljinskaya, O.; Tararak, E.; Bochkov, V.; Erne, P.; Resink, T.; Tkachuk, V. Expression of Cell Adhesion Molecule T-Cadherin in the Human Vasculature. Histochem. Cell Biol. 2001, 115, 231–242. [Google Scholar] [CrossRef]
- Kudrjashova, E.; Bashtrikov, P.; Bochkov, V.; Parfyonova, Y.; Tkachuk, V.; Antropova, J.; Iljinskaya, O.; Tararak, E.; Erne, P.; Ivanov, D.; et al. Expression of Adhesion Molecule T-Cadherin Is Increased during Neointima Formation in Experimental Restenosis. Histochem. Cell Biol. 2002, 118, 281–290. [Google Scholar] [CrossRef] [PubMed]
- Rubina, K.; Sysoeva, V.; Semina, E.; Kalinina, N.; Yurlova, E.; Khlebnikova, A.; Molochkov, V.; Rubina, K.; Sysoeva, V.; Semina, E.; et al. Malignant Transformation in Skin Is Associated with the Loss of T-Cadherin Expression in Human Keratinocytes and Heterogeneity in T-Cadherin Expression in Tumor Vasculature. In Tumor Angiogenesis; IntechOpen: London, UK, 2012; ISBN 978-953-51-0009-6. [Google Scholar]
- Parker-Duffen, J.L.; Nakamura, K.; Silver, M.; Kikuchi, R.; Tigges, U.; Yoshida, S.; Denzel, M.S.; Ranscht, B.; Walsh, K. T-Cadherin Is Essential for Adiponectin-Mediated Revascularization. J. Biol. Chem. 2013, 288, 24886–24897. [Google Scholar] [CrossRef]
- Tsugawa-Shimizu, Y.; Fujishima, Y.; Kita, S.; Minami, S.; Sakaue, T.-A.; Nakamura, Y.; Okita, T.; Kawachi, Y.; Fukada, S.; Namba-Hamano, T.; et al. Increased Vascular Permeability and Severe Renal Tubular Damage after Ischemia-Reperfusion Injury in Mice Lacking Adiponectin or T-Cadherin. Am. J. Physiol. Endocrinol. Metab. 2021, 320, E179–E190. [Google Scholar] [CrossRef]
- Hebbard, L.; Ranscht, B. Multifaceted Roles of Adiponectin in Cancer. Best Pract. Res. Clin. Endocrinol. Metab. 2014, 28, 59–69. [Google Scholar] [CrossRef] [PubMed]
- Rubina, K.A.; Surkova, E.I.; Semina, E.V.; Sysoeva, V.Y.; Kalinina, N.I.; Poliakov, A.A.; Treshalina, H.M.; Tkachuk, V.A. T-Cadherin Expression in Melanoma Cells Stimulates Stromal Cell Recruitment and Invasion by Regulating the Expression of Chemokines, Integrins and Adhesion Molecules. Cancers 2015, 7, 1349–1370. [Google Scholar] [CrossRef] [PubMed]
- Wen, Y.; Ma, L.; Liu, Y.; Xiong, H.; Shi, D. Decoding the Enigmatic Role of T-Cadherin in Tumor Angiogenesis. Front. Immunol. 2025, 16, 1564130. [Google Scholar] [CrossRef]
- Sternberg, J.; Wankell, M.; Subramaniam, V.N.; Hebbard, L.W.; Sternberg, J.; Wankell, M.; Subramaniam, V.N.; Hebbard, L.W. The Functional Roles of T-Cadherin in Mammalian Biology. Aimsmoles 2017, 4, 62–81. [Google Scholar] [CrossRef]
- Fukuda, S.; Kita, S.; Miyashita, K.; Iioka, M.; Murai, J.; Nakamura, T.; Nishizawa, H.; Fujishima, Y.; Morinaga, J.; Oike, Y.; et al. Identification and Clinical Associations of 3 Forms of Circulating T-Cadherin in Human Serum. J. Clin. Endocrinol. Metab. 2021, 106, 1333–1344. [Google Scholar] [CrossRef]
- Yang, Y.R.; Kabir, M.H.; Park, J.H.; Park, J.-I.; Kang, J.S.; Ju, S.; Shin, Y.J.; Lee, S.M.; Lee, J.; Kim, S.; et al. Plasma Proteomic Profiling of Young and Old Mice Reveals Cadherin-13 Prevents Age-Related Bone Loss. Aging 2020, 12, 8652–8668. [Google Scholar] [CrossRef]
- Frismantiene, A.; Dasen, B.; Pfaff, D.; Erne, P.; Resink, T.J.; Philippova, M. T-Cadherin Promotes Vascular Smooth Muscle Cell Dedifferentiation via a GSK3β-Inactivation Dependent Mechanism. Cell. Signal. 2016, 28, 516–530. [Google Scholar] [CrossRef]
- Kyriakakis, E.; Frismantiene, A.; Dasen, B.; Pfaff, D.; Rivero, O.; Lesch, K.-P.; Erne, P.; Resink, T.J.; Philippova, M. T-Cadherin Promotes Autophagy and Survival in Vascular Smooth Muscle Cells through MEK1/2/Erk1/2 Axis Activation. Cell. Signal. 2017, 35, 163–175. [Google Scholar] [CrossRef]
- Otsuka, I.; Watanabe, Y.; Hishimoto, A.; Boku, S.; Mouri, K.; Shiroiwa, K.; Okazaki, S.; Nunokawa, A.; Shirakawa, O.; Someya, T.; et al. Association Analysis of the Cadherin13 Gene with Schizophrenia in the Japanese Population. Neuropsychiatr. Dis. Treat. 2015, 11, 1381–1393. [Google Scholar] [CrossRef] [PubMed]
- Gupta, S.; Priya, I.; Arora, M.; Singh, H.; Sharma, I.; Sharma, S.; Mahajan, R.; Kapoor, N. Association of the CDH13 Gene Variant Rs9940180 with Schizophrenia Risk in North Indian Population. Am. J. Transl. Res. 2023, 15, 6476–6485. [Google Scholar] [PubMed]
- Kiser, D.P.; Popp, S.; Schmitt-Böhrer, A.G.; Strekalova, T.; van den Hove, D.L.; Lesch, K.-P.; Rivero, O. Early-Life Stress Impairs Developmental Programming in Cadherin 13 (CDH13)-Deficient Mice. Progress. Neuro-Psychopharmacol. Biol. Psychiatry 2019, 89, 158–168. [Google Scholar] [CrossRef] [PubMed]
- Mossink, B.; van Rhijn, J.-R.; Wang, S.; Linda, K.; Vitale, M.R.; Zöller, J.E.M.; van Hugte, E.J.H.; Bak, J.; Verboven, A.H.A.; Selten, M.; et al. Cadherin-13 Is a Critical Regulator of GABAergic Modulation in Human Stem-Cell-Derived Neuronal Networks. Mol. Psychiatry 2022, 27, 1–18. [Google Scholar] [CrossRef]
- Sanders, S.J.; He, X.; Willsey, A.J.; Ercan-Sencicek, A.G.; Samocha, K.E.; Cicek, A.E.; Murtha, M.T.; Bal, V.H.; Bishop, S.L.; Dong, S.; et al. Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci. Neuron 2015, 87, 1215–1233. [Google Scholar] [CrossRef]
- Asherson, P.; Zhou, K.; Anney, R.J.L.; Franke, B.; Buitelaar, J.; Ebstein, R.; Gill, M.; Altink, M.; Arnold, R.; Boer, F.; et al. A High-Density SNP Linkage Scan with 142 Combined Subtype ADHD Sib Pairs Identifies Linkage Regions on Chromosomes 9 and 16. Mol. Psychiatry 2008, 13, 514–521. [Google Scholar] [CrossRef]
- Neale, B.M.; Medland, S.E.; Ripke, S.; Asherson, P.; Franke, B.; Lesch, K.-P.; Faraone, S.V.; Nguyen, T.T.; Schäfer, H.; Holmans, P.; et al. Meta-Analysis of Genome-Wide Association Studies of Attention-Deficit/Hyperactivity Disorder. J. Am. Acad. Child Adolesc. Psychiatry 2010, 49, 884–897. [Google Scholar] [CrossRef]
- Treutlein, J.; Cichon, S.; Ridinger, M.; Wodarz, N.; Soyka, M.; Zill, P.; Maier, W.; Moessner, R.; Gaebel, W.; Dahmen, N.; et al. Genome-Wide Association Study of Alcohol Dependence. Arch. Gen. Psychiatry 2009, 66, 773–784. [Google Scholar] [CrossRef]
- Sarı, E.; Erbaş, O. Non-Coding RNA and Functions. JEBMS 2021, 2, 128–132. [Google Scholar] [CrossRef]
- Hombach, S.; Kretz, M. Non-Coding RNAs: Classification, Biology and Functioning. Adv. Exp. Med. Biol. 2016, 937, 3–17. [Google Scholar] [CrossRef] [PubMed]
- Zhang, P.; Wu, W.; Chen, Q.; Chen, M. Non-Coding RNAs and Their Integrated Networks. J. Integr. Bioinform. 2019, 16, 20190027. [Google Scholar] [CrossRef]
- Mattick, J.S.; Amaral, P.P.; Carninci, P.; Carpenter, S.; Chang, H.Y.; Chen, L.-L.; Chen, R.; Dean, C.; Dinger, M.E.; Fitzgerald, K.A.; et al. Long Non-Coding RNAs: Definitions, Functions, Challenges and Recommendations. Nat. Rev. Mol. Cell Biol. 2023, 24, 430–447. [Google Scholar] [CrossRef]
- Chellini, L.; Frezza, V.; Paronetto, M.P. Dissecting the Transcriptional Regulatory Networks of Promoter-Associated Noncoding RNAs in Development and Cancer. J. Exp. Clin. Cancer Res. 2020, 39, 51. [Google Scholar] [CrossRef]
- Robinson, E.K.; Covarrubias, S.; Carpenter, S. The How and Why of lncRNA Function: An Innate Immune Perspective. Biochim. Biophys. Acta Gene Regul. Mech. 2020, 1863, 194419. [Google Scholar] [CrossRef] [PubMed]
- Kumar, P.; Bhandari, N.; Kumar, P.; Bhandari, N. lncRNAs: Role in Regulation of Gene Expression. In Gene Expression; IntechOpen: Lundon, UK, 2022; ISBN 978-1-80355-622-2. [Google Scholar]
- Wang, X.; Li, H.; Lu, Y.; Cheng, L. Regulatory Effects of Circular RNAs on Host Genes in Human Cancer. Front. Oncol. 2021, 10, 586163. [Google Scholar] [CrossRef]
- Lau, P.-W.; Guiley, K.Z.; De, N.; Potter, C.S.; Carragher, B.; MacRae, I.J. The Molecular Architecture of Human Dicer. Nat. Struct. Mol. Biol. 2012, 19, 436–440. [Google Scholar] [CrossRef] [PubMed]
- Schanen, B.C.; Li, X. Transcriptional Regulation of Mammalian miRNA Genes. Genomics 2011, 97, 1–6. [Google Scholar] [CrossRef]
- MacFarlane, L.-A.; Murphy, P.R. MicroRNA: Biogenesis, Function and Role in Cancer. Curr. Genom. 2010, 11, 537–561. [Google Scholar] [CrossRef]
- Hammond, S.M. An Overview of microRNAs. Adv. Drug Deliv. Rev. 2015, 87, 3–14. [Google Scholar] [CrossRef]
- Maia, J.; Caja, S.; Strano Moraes, M.C.; Couto, N.; Costa-Silva, B. Exosome-Based Cell-Cell Communication in the Tumor Microenvironment. Front. Cell Dev. Biol. 2018, 6, 18. [Google Scholar] [CrossRef] [PubMed]
- Oh, H.J.; Aguilar, R.; Kesner, B.; Lee, H.-G.; Kriz, A.J.; Chu, H.-P.; Lee, J.T. Jpx RNA Regulates CTCF Anchor Site Selection and Formation of Chromosome Loops. Cell 2021, 184, 6157–6173.e24. [Google Scholar] [CrossRef]
- Granados-Riveron, J.T.; Aquino-Jarquin, G. The Complexity of the Translation Ability of circRNAs. Biochim. Biophys. Acta (BBA)-Gene Regul. Mech. 2016, 1859, 1245–1251. [Google Scholar] [CrossRef] [PubMed]
- Ashwal-Fluss, R.; Meyer, M.; Pamudurti, N.R.; Ivanov, A.; Bartok, O.; Hanan, M.; Evantal, N.; Memczak, S.; Rajewsky, N.; Kadener, S. circRNA Biogenesis Competes with Pre-mRNA Splicing. Mol. Cell 2014, 56, 55–66. [Google Scholar] [CrossRef]
- Belousova, E.A.; Filipenko, M.L.; Kushlinskii, N.E. Circular RNA: New Regulatory Molecules. Bull. Exp. Biol. Med. 2018, 164, 803–815. [Google Scholar] [CrossRef] [PubMed]
- Hansen, T.B.; Jensen, T.I.; Clausen, B.H.; Bramsen, J.B.; Finsen, B.; Damgaard, C.K.; Kjems, J. Natural RNA Circles Function as Efficient microRNA Sponges. Nature 2013, 495, 384–388. [Google Scholar] [CrossRef]
- Zhang, Y.; Zhao, Y.; Ao, X.; Yu, W.; Zhang, L.; Wang, Y.; Chang, W. The Role of Non-Coding RNAs in Alzheimer’s Disease: From Regulated Mechanism to Therapeutic Targets and Diagnostic Biomarkers. Front. Aging Neurosci. 2021, 13, 654978. [Google Scholar] [CrossRef]
- Xiao, J. (Ed.) Circular RNAs: Biogenesis and Functions; Advances in Experimental Medicine and Biology; Springer: Singapore, 2018; ISBN 9789811314254. [Google Scholar]
- de Rie, D.; Abugessaisa, I.; Alam, T.; Arner, E.; Arner, P.; Ashoor, H.; Åström, G.; Babina, M.; Bertin, N.; Burroughs, A.M.; et al. An Integrated Expression Atlas of miRNAs and Their Promoters in Human and Mouse. Nat. Biotechnol. 2017, 35, 872–878. [Google Scholar] [CrossRef]
- Ozsolak, F.; Poling, L.L.; Wang, Z.; Liu, H.; Liu, X.S.; Roeder, R.G.; Zhang, X.; Song, J.S.; Fisher, D.E. Chromatin Structure Analyses Identify miRNA Promoters. Genes. Dev. 2008, 22, 3172–3183. [Google Scholar] [CrossRef] [PubMed]
- Ha, M.; Kim, V.N. Regulation of microRNA Biogenesis. Nat. Rev. Mol. Cell Biol. 2014, 15, 509–524. [Google Scholar] [CrossRef]
- Martin, J.; Han, C.; Gordon, L.A.; Terry, A.; Prabhakar, S.; She, X.; Xie, G.; Hellsten, U.; Chan, Y.M.; Altherr, M.; et al. The Sequence and Analysis of Duplication-Rich Human Chromosome 16. Nature 2004, 432, 988–994. [Google Scholar] [CrossRef] [PubMed]
- Zhu, Y.; Xie, J.; Sun, H. Three miRNAs Cooperate with Host Genes Involved in Human Cardiovascular Disease. Hum. Genom. 2019, 13, 40. [Google Scholar] [CrossRef]
- Chien, K.R.; Olson, E.N. Converging Pathways and Principles in Heart Development and Disease: CV@CSH. Cell 2002, 110, 153–162. [Google Scholar] [CrossRef]
- Ramos-Kuri, M.; Meka, S.H.; Salamanca-Buentello, F.; Hajjar, R.J.; Lipskaia, L.; Chemaly, E.R. Molecules Linked to Ras Signaling as Therapeutic Targets in Cardiac Pathologies. Biol. Res. 2021, 54, 23. [Google Scholar] [CrossRef]
- Wang, H.; Zhang, P.; Chen, W.; Jie, D.; Dan, F.; Jia, Y.; Xie, L. Characterization and Identification of Novel Serum microRNAs in Sepsis Patients with Different Outcomes. Shock 2013, 39, 480–487. [Google Scholar] [CrossRef]
- Griffiths-Jones, S.; Grocock, R.J.; van Dongen, S.; Bateman, A.; Enright, A.J. miRBase: MicroRNA Sequences, Targets and Gene Nomenclature. Nucleic Acids Res. 2006, 34, D140–D144. [Google Scholar] [CrossRef] [PubMed]
- Stark, M.S.; Tyagi, S.; Nancarrow, D.J.; Boyle, G.M.; Cook, A.L.; Whiteman, D.C.; Parsons, P.G.; Schmidt, C.; Sturm, R.A.; Hayward, N.K. Characterization of the Melanoma miRNAome by Deep Sequencing. PLoS ONE 2010, 5, e9685. [Google Scholar] [CrossRef] [PubMed]
- Issler, O.; van der Zee, Y.Y.; Ramakrishnan, A.; Xia, S.; Zinsmaier, A.K.; Tan, C.; Li, W.; Browne, C.J.; Walker, D.M.; Salery, M.; et al. The Long Noncoding RNA FEDORA Is a Cell Type- and Sex-Specific Regulator of Depression. Sci. Adv. 2022, 8, eabn9494. [Google Scholar] [CrossRef]
- Cai, M.; Wang, Y.-W.; Xu, S.-H.; Qiao, S.; Shu, Q.-F.; Du, J.-Z.; Li, Y.-G.; Liu, X.-L. Regulatory Effects of the Long Non-coding RNA RP11-543N12.1 and microRNA-324-3p Axis on the Neuronal Apoptosis Induced by the Inflammatory Reactions of Microglia. Int. J. Mol. Med. 2018, 42, 1741–1755. [Google Scholar] [CrossRef]
- Wang, L.-K.; Chen, X.-F.; He, D.-D.; Li, Y.; Fu, J. Dissection of Functional lncRNAs in Alzheimer’s Disease by Construction and Analysis of lncRNA–mRNA Networks Based on Competitive Endogenous RNAs. Biochem. Biophys. Res. Commun. 2017, 485, 569–576. [Google Scholar] [CrossRef]
- Xu, J.; Ai, Q.; Cao, H.; Liu, Q. MiR-185-3p and miR-324-3p Predict Radiosensitivity of Nasopharyngeal Carcinoma and Modulate Cancer Cell Growth and Apoptosis by Targeting SMAD7. Med. Sci. Monit. 2015, 21, 2828–2836. [Google Scholar] [CrossRef] [PubMed]
- Chen, Z.; Li, S.; Li, L.; Diagel, A.; Moggio, A.; Li, Z.; Song, X.; Sager, H.; Boon, R.; Maegdefessel, L.; et al. The Orchestration of Coding and Non-Coding Genes at the CDH13 Locus in Coronary Artery Disease. Eur. Heart J. 2024, 45, ehae666.3831. [Google Scholar] [CrossRef]
- Zhou, Z.; Ma, J.; Lu, J.; Chen, A.; Zhu, L. Circular RNA CircCDH13 Contributes to the Pathogenesis of Osteoarthritis via CircCDH13/miR-296-3p/PTEN Axis. J. Cell Physiol. 2021, 236, 3521–3535. [Google Scholar] [CrossRef]
- Mao, X.; Cao, Y.; Guo, Z.; Wang, L.; Xiang, C. Biological Roles and Therapeutic Potential of Circular RNAs in Osteoarthritis. Mol. Ther.-Nucleic Acids 2021, 24, 856–867. [Google Scholar] [CrossRef]
- Bromhead, C.; Miller, J.H.; McDonald, F.J. Regulation of T-Cadherin by Hormones, Glucocorticoid and EGF. Gene 2006, 374, 58–67. [Google Scholar] [CrossRef]
- Kuzmenko, Y.S.; Kern, F.; Bochkov, V.N.; Tkachuk, V.A.; Resink, T.J. Density- and Proliferation Status-Dependent Expression of T-Cadherin, a Novel Lipoprotein-Binding Glycoprotein: A Function in Negative Regulation of Smooth Muscle Cell Growth? FEBS Lett. 1998, 434, 183–187. [Google Scholar] [CrossRef] [PubMed]
- Kuzmenko, Y.S.; Stambolsky, D.; Kern, F.; Bochkov, V.N.; Tkachuk, V.A.; Resink, T.J. Characteristics of Smooth Muscle Cell Lipoprotein Binding Proteins (P105/P130) as T-Cadherin and Regulation by Positive and Negative Growth Regulators. Biochem. Biophys. Res. Commun. 1998, 246, 489–494. [Google Scholar] [CrossRef]
- Wang, Y.; Zhang, L.; Yang, J.; Li, B.; Wang, J. CDH13 Promoter Methylation Regulates Cisplatin Resistance of Non-Small Cell Lung Cancer Cells. Oncol. Lett. 2018, 16, 5715–5722. [Google Scholar] [CrossRef]
- Shiu, B.-H.; Lu, W.-Y.; Tantoh, D.M.; Chou, M.-C.; Nfor, O.N.; Huang, C.-C.; Liaw, Y.-P. Interactive Association between Dietary Fat and Sex on CDH13 Cg02263260 Methylation. BMC Med. Genom. 2021, 14, 13. [Google Scholar] [CrossRef]
- Pu, W.; Geng, X.; Chen, S.; Tan, L.; Tan, Y.; Wang, A.; Lu, Z.; Guo, S.; Chen, X.; Wang, J. Aberrant Methylation of CDH13 Can Be a Diagnostic Biomarker for Lung Adenocarcinoma. J. Cancer 2016, 7, 2280–2289. [Google Scholar] [CrossRef]
- Ellmann, L.; Joshi, M.B.; Resink, T.J.; Bosserhoff, A.K.; Kuphal, S. BRN2 Is a Transcriptional Repressor of CDH13 (T-Cadherin) in Melanoma Cells. Lab. Investig. 2012, 92, 1788–1800. [Google Scholar] [CrossRef] [PubMed]
- Favreau, A.J.; McGlauflin, R.E.; Duarte, C.W.; Sathyanarayana, P. miR-199b, a Novel Tumor Suppressor miRNA in Acute Myeloid Leukemia with Prognostic Implications. Exp. Hematol. Oncol. 2015, 5, 4. [Google Scholar] [CrossRef]
- Ragusa, R.; Di Molfetta, A.; Mercatanti, A.; Pitto, L.; Amodeo, A.; Trivella, M.G.; Rizzo, M.; Caselli, C. Changes in Adiponectin System after Ventricular Assist Device in Pediatric Heart Failure. JHLT Open 2024, 3, 100041. [Google Scholar] [CrossRef] [PubMed]
- Wang, C.; Song, B.; Song, W.; Liu, J.; Sun, A.; Wu, D.; Yu, H.; Lian, J.; Chen, L.; Han, J. Underexpressed microRNA-199b-5p Targets Hypoxia-Inducible Factor-1α in Hepatocellular Carcinoma and Predicts Prognosis of Hepatocellular Carcinoma Patients. J. Gastroenterol. Hepatol. 2011, 26, 1630–1637. [Google Scholar] [CrossRef] [PubMed]
- Shang, W.; Chen, X.; Nie, L.; Xu, M.; Chen, N.; Zeng, H.; Zhou, Q. MiR199b Suppresses Expression of Hypoxia-Inducible Factor 1α (HIF-1α) in Prostate Cancer Cells. Int. J. Mol. Sci. 2013, 14, 8422–8436. [Google Scholar] [CrossRef] [PubMed]
- Fang, C.; Zhao, Y.; Guo, B. MiR-199b-5p Targets HER2 in Breast Cancer Cells. J. Cell Biochem. 2013, 114, 1457–1463. [Google Scholar] [CrossRef]
- Joshi, D.; Chandrakala, S.; Korgaonkar, S.; Ghosh, K.; Vundinti, B.R. Down-Regulation of miR-199b Associated with Imatinib Drug Resistance in 9q34.1 Deleted BCR/ABL Positive CML Patients. Gene 2014, 542, 109–112. [Google Scholar] [CrossRef]
- Liu, M.X.; Siu, M.K.Y.; Liu, S.S.; Yam, J.W.P.; Ngan, H.Y.S.; Chan, D.W. Epigenetic Silencing of microRNA-199b-5p Is Associated with Acquired Chemoresistance via Activation of JAG1-Notch1 Signaling in Ovarian Cancer. Oncotarget 2014, 5, 944–958. [Google Scholar] [CrossRef]
- Garzia, L.; Andolfo, I.; Cusanelli, E.; Marino, N.; Petrosino, G.; De Martino, D.; Esposito, V.; Galeone, A.; Navas, L.; Esposito, S.; et al. MicroRNA-199b-5p Impairs Cancer Stem Cells through Negative Regulation of HES1 in Medulloblastoma. PLoS ONE 2009, 4, e4998. [Google Scholar] [CrossRef]
- Wyder, L.; Vitaliti, A.; Schneider, H.; Hebbard, L.W.; Moritz, D.R.; Wittmer, M.; Ajmo, M.; Klemenz, R. Increased Expression of H/T-Cadherin in Tumor-Penetrating Blood Vessels. Cancer Res. 2000, 60, 4682–4688. [Google Scholar]
- Whitehead, J.P.; Richards, A.A.; Hickman, I.J.; Macdonald, G.A.; Prins, J.B. Adiponectin—A Key Adipokine in the Metabolic Syndrome. Diabetes Obes. Metab. 2006, 8, 264–280. [Google Scholar] [CrossRef] [PubMed]
- Achari, A.E.; Jain, S.K. Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction. Int. J. Mol. Sci. 2017, 18, 1321. [Google Scholar] [CrossRef]
- Baltrūnienė, V.; Rinkūnaitė, I.; Bogomolovas, J.; Bironaitė, D.; Kažukauskienė, I.; Šimoliūnas, E.; Ručinskas, K.; Puronaitė, R.; Bukelskienė, V.; Grabauskienė, A.V. The Role of Cardiac T-Cadherin in the Indicating Heart Failure Severity of Patients with Non-Ischemic Dilated Cardiomyopathy. Medicina 2020, 56, 27. [Google Scholar] [CrossRef] [PubMed]
- Li, W.; Li, K.; Wang, Z.; Fa, Z. MicroRNA-377-3p Promotes Cell Proliferation and Inhibits Cell Cycle Arrest and Cell Apoptosis in Hepatocellular Carcinoma by Affecting EGR1-Mediated P53 Activation. Pathol.-Res. Pract. 2022, 234, 153855. [Google Scholar] [CrossRef] [PubMed]
- Di Palo, A.; Siniscalchi, C.; Polito, R.; Nigro, E.; Russo, A.; Daniele, A.; Potenza, N. microRNA-377-3p Downregulates the Oncosuppressor T-cadherin in Colorectal Adenocarcinoma Cells. Cell Biol. Int. 2021, 45, 1797–1803. [Google Scholar] [CrossRef]
- Liu, F.-F.; Zhang, Z.; Chen, W.; Gu, H.-Y.; Yan, Q.-J. Regulatory Mechanism of microRNA-377 on CDH13 Expression in the Cell Model of Alzheimer’s Disease. Eur. Rev. Med. Pharmacol. Sci. 2018, 22, 2801–2808. [Google Scholar] [CrossRef]
- Dalamaga, M.; Diakopoulos, K.N.; Mantzoros, C.S. The Role of Adiponectin in Cancer: A Review of Current Evidence. Endocr. Rev. 2012, 33, 547–594. [Google Scholar] [CrossRef]
- Hefetz-Sela, S.; Scherer, P.E. Adipocytes: Impact on Tumor Growth and Potential Sites for Therapeutic Intervention. Pharmacol. Ther. 2013, 138, 197–210. [Google Scholar] [CrossRef]
- Otake, S.; Takeda, H.; Suzuki, Y.; Fukui, T.; Watanabe, S.; Ishihama, K.; Saito, T.; Togashi, H.; Nakamura, T.; Matsuzawa, Y.; et al. Association of Visceral Fat Accumulation and Plasma Adiponectin with Colorectal Adenoma: Evidence for Participation of Insulin Resistance. Clin. Cancer Res. 2005, 11, 3642–3646. [Google Scholar] [CrossRef]
- Ishikawa, M.; Kitayama, J.; Kazama, S.; Hiramatsu, T.; Hatano, K.; Nagawa, H. Plasma Adiponectin and Gastric Cancer. Clin. Cancer Res. 2005, 11, 466–472. [Google Scholar] [CrossRef]
- Otani, K.; Ishihara, S.; Yamaguchi, H.; Murono, K.; Yasuda, K.; Nishikawa, T.; Tanaka, T.; Kiyomatsu, T.; Hata, K.; Kawai, K.; et al. Adiponectin and Colorectal Cancer. Surg. Today 2017, 47, 151–158. [Google Scholar] [CrossRef]
- Polito, R.; Nigro, E.; Fei, L.; DE Magistris, L.; Monaco, M.L.; D’Amico, R.; Naviglio, S.; Signoriello, G.; Daniele, A. Adiponectin Is Inversely Associated With Tumour Grade in Colorectal Cancer Patients. Anticancer Res. 2020, 40, 3751–3757. [Google Scholar] [CrossRef]
- Liu, W.-Y.; Yang, Z.; Sun, Q.; Yang, X.; Hu, Y.; Xie, H.; Gao, H.-J.; Guo, L.-M.; Yi, J.-Y.; Liu, M.; et al. miR-377-3p Drives Malignancy Characteristics via Upregulating GSK-3β Expression and Activating NF-κB Pathway in hCRC Cells. J. Cell Biochem. 2018, 119, 2124–2134. [Google Scholar] [CrossRef] [PubMed]
- Peng, J.; Wu, Y.; Deng, Z.; Zhou, Y.; Song, T.; Yang, Y.; Zhang, X.; Xu, T.; Xia, M.; Cai, A.; et al. MiR-377 Promotes White Adipose Tissue Inflammation and Decreases Insulin Sensitivity in Obesity via Suppression of Sirtuin-1 (SIRT1). Oncotarget 2017, 8, 70550–70563. [Google Scholar] [CrossRef] [PubMed]
- Huang, Z.; Wu, Y.; Hedrick, N.; Gutmann, D.H. T-Cadherin-Mediated Cell Growth Regulation Involves G2 Phase Arrest and Requires P21(CIP1/WAF1) Expression. Mol. Cell Biol. 2003, 23, 566–578. [Google Scholar] [CrossRef]
- Li, L.; Gao, Y.; Yu, B.; Zhang, J.; Ma, G.; Jin, X. Role of LncRNA H19 in Tumor Progression and Treatment. Mol. Cell Probes 2024, 75, 101961. [Google Scholar] [CrossRef] [PubMed]
- Keniry, A.; Oxley, D.; Monnier, P.; Kyba, M.; Dandolo, L.; Smits, G.; Reik, W. The H19 lincRNA Is a Developmental Reservoir of miR-675 That Suppresses Growth and Igf1r. Nat. Cell Biol. 2012, 14, 659–665. [Google Scholar] [CrossRef]
- Shi, Y.; Wang, Y.; Luan, W.; Wang, P.; Tao, T.; Zhang, J.; Qian, J.; Liu, N.; You, Y. Long Non-Coding RNA H19 Promotes Glioma Cell Invasion by Deriving miR-675. PLoS ONE 2014, 9, e86295. [Google Scholar] [CrossRef]
- Li, L.; Chen, W.; Wang, Y.; Tang, L.; Han, M. Long Non-Coding RNA H19 Regulates Viability and Metastasis, and Is Upregulated in Retinoblastoma. Oncol. Lett. 2018, 15, 8424–8432. [Google Scholar] [CrossRef]
- Liang, W.-C.; Fu, W.-M.; Wong, C.-W.; Wang, Y.; Wang, W.-M.; Hu, G.-X.; Zhang, L.; Xiao, L.-J.; Wan, D.C.-C.; Zhang, J.-F.; et al. The lncRNA H19 Promotes Epithelial to Mesenchymal Transition by Functioning as miRNA Sponges in Colorectal Cancer. Oncotarget 2015, 6, 22513–22525. [Google Scholar] [CrossRef]
- Lin, R.-K.; Hsu, H.-S.; Chang, J.-W.; Chen, C.-Y.; Chen, J.-T.; Wang, Y.-C. Alteration of DNA Methyltransferases Contributes to 5′CpG Methylation and Poor Prognosis in Lung Cancer. Lung Cancer 2007, 55, 205–213. [Google Scholar] [CrossRef] [PubMed]
- Yang, H.; Liu, Y.; Bai, F.; Zhang, J.-Y.; Ma, S.-H.; Liu, J.; Xu, Z.-D.; Zhu, H.-G.; Ling, Z.-Q.; Ye, D.; et al. Tumor Development Is Associated with Decrease of TET Gene Expression and 5-Methylcytosine Hydroxylation. Oncogene 2013, 32, 663–669. [Google Scholar] [CrossRef] [PubMed]
- Masalmeh, R.H.A.; Taglini, F.; Rubio-Ramon, C.; Musialik, K.I.; Higham, J.; Davidson-Smith, H.; Kafetzopoulos, I.; Pawlicka, K.P.; Finan, H.M.; Clark, R.; et al. De Novo DNA Methyltransferase Activity in Colorectal Cancer Is Directed towards H3K36me3 Marked CpG Islands. Nat. Commun. 2021, 12, 694. [Google Scholar] [CrossRef]
- Maćkowska, N.; Drobna-Śledzińska, M.; Witt, M.; Dawidowska, M. DNA Methylation in T-Cell Acute Lymphoblastic Leukemia: In Search for Clinical and Biological Meaning. Int. J. Mol. Sci. 2021, 22, 1388. [Google Scholar] [CrossRef] [PubMed]
- Fan, X.; Tao, S.; Li, Q.; Deng, B.; Tan, Q.-Y.; Jin, H. The miR-23a/27a/24-2 Cluster Promotes Postoperative Progression of Early-Stage Non-Small Cell Lung Cancer. Mol. Ther.-Oncolytics 2022, 24, 205–217. [Google Scholar] [CrossRef]
- Zareifar, P.; Ahmed, H.M.; Ghaderi, P.; Farahmand, Y.; Rahnama, N.; Esbati, R.; Moradi, A.; Yazdani, O.; Sadeghipour, Y. miR-142-3p/5p Role in Cancer: From Epigenetic Regulation to Immunomodulation. Cell Biochem. Funct. 2024, 42, e3931. [Google Scholar] [CrossRef]
- Ma, G.; Li, Y.; Meng, F.; Sui, C.; Wang, Y.; Cheng, D. Hsa_circ_0000119 Promoted Ovarian Cancer Development via Enhancing the Methylation of CDH13 by Sponging miR-142-5p. J. Biochem. Mol. Toxicol. 2023, 37, e23264. [Google Scholar] [CrossRef]
- Wang, H.; Cao, D.; Wu, F. Long Noncoding RNA UPAT Promoted Cell Proliferation via Increasing UHRF1 Expression in Non-Small Cell Lung Cancer. Oncol. Lett. 2018, 16, 1491–1498. [Google Scholar] [CrossRef]
- Taniue, K.; Kurimoto, A.; Sugimasa, H.; Nasu, E.; Takeda, Y.; Iwasaki, K.; Nagashima, T.; Okada-Hatakeyama, M.; Oyama, M.; Kozuka-Hata, H.; et al. Long Noncoding RNA UPAT Promotes Colon Tumorigenesis by Inhibiting Degradation of UHRF1. Proc. Natl. Acad. Sci. USA 2016, 113, 1273–1278. [Google Scholar] [CrossRef]
- Tan, W.-H.; Peng, Z.-L.; You, T.; Sun, Z.-L. CTRP15 Promotes Macrophage Cholesterol Efflux and Attenuates Atherosclerosis by Increasing the Expression of ABCA1. J. Physiol. Biochem. 2022, 78, 653–666. [Google Scholar] [CrossRef]
- Seldin, M.M.; Peterson, J.M.; Byerly, M.S.; Wei, Z.; Wong, G.W. Myonectin (CTRP15), a Novel Myokine That Links Skeletal Muscle to Systemic Lipid Homeostasis. J. Biol. Chem. 2012, 287, 11968–11980. [Google Scholar] [CrossRef]
- Cai, Y.; Liu, J.; Cai, S.-K.; Miao, E.-Y.; Jia, C.-Q.; Fan, Y.-Z.; Li, Y.-B. Eicosapentaenoic Acid’s Metabolism of 15-LOX-1 Promotes the Expression of miR-101 Thus Inhibits Cox2 Pathway in Colon Cancer. OncoTargets Ther. 2020, 13, 5605–5616. [Google Scholar] [CrossRef] [PubMed]
- Liu, P.; Ye, F.; Xie, X.; Li, X.; Tang, H.; Li, S.; Huang, X.; Song, C.; Wei, W.; Xie, X. Mir-101-3p Is a Key Regulator of Tumor Metabolism in Triple Negative Breast Cancer Targeting AMPK. Oncotarget 2016, 7, 35188–35198. [Google Scholar] [CrossRef] [PubMed]
- Rincón-Riveros, A.; Morales, D.; Rodríguez, J.A.; Villegas, V.E.; López-Kleine, L. Bioinformatic Tools for the Analysis and Prediction of ncRNA Interactions. Int. J. Mol. Sci. 2021, 22, 11397. [Google Scholar] [CrossRef]
- Wang, H.; Mazzocca, A.; Gao, P. Cadherin Dysregulation in Gastric Cancer: Insights into Gene Expression, Pathways, and Prognosis. J. Gastrointest. Oncol. 2023, 14, 2064–2082. [Google Scholar] [CrossRef] [PubMed]
- Coban, N.; Pirim, D.; Erkan, A.F.; Dogan, B.; Ekici, B. Hsa-miR-584-5p as a Novel Candidate Biomarker in Turkish Men with Severe Coronary Artery Disease. Mol. Biol. Rep. 2020, 47, 1361–1369. [Google Scholar] [CrossRef]
- Lee, H.; Park, C.S.; Deftereos, G.; Morihara, J.; Stern, J.E.; Hawes, S.E.; Swisher, E.; Kiviat, N.B.; Feng, Q. MicroRNA Expression in Ovarian Carcinoma and Its Correlation with Clinicopathological Features. World J. Surg. Oncol. 2012, 10, 174. [Google Scholar] [CrossRef]
- Feng, Q.; Deftereos, G.; Hawes, S.E.; Stern, J.E.; Willner, J.B.; Swisher, E.M.; Xi, L.; Drescher, C.; Urban, N.; Kiviat, N. DNA Hypermethylation, Her-2/Neu Overexpression and P53 Mutations in Ovarian Carcinoma. Gynecol. Oncol. 2008, 111, 320–329. [Google Scholar] [CrossRef]
- Ducoli, L.; Agrawal, S.; Sibler, E.; Kouno, T.; Tacconi, C.; Hon, C.-C.; Berger, S.D.; Müllhaupt, D.; He, Y.; Kim, J.; et al. LETR1 Is a Lymphatic Endothelial-Specific lncRNA Governing Cell Proliferation and Migration through KLF4 and SEMA3C. Nat. Commun. 2021, 12, 925. [Google Scholar] [CrossRef]
- David, C.J.; Massagué, J. Contextual Determinants of TGFβ Action in Development, Immunity and Cancer. Nat. Rev. Mol. Cell Biol. 2018, 19, 419–435. [Google Scholar] [CrossRef]
- Heldin, C.-H.; Vanlandewijck, M.; Moustakas, A. Regulation of EMT by TGFβ in Cancer. FEBS Lett. 2012, 586, 1959–1970. [Google Scholar] [CrossRef] [PubMed]
- Gélabert, C.; Papoutsoglou, P.; Golán, I.; Ahlström, E.; Ameur, A.; Heldin, C.-H.; Caja, L.; Moustakas, A. The Long Non-Coding RNA LINC00707 Interacts with Smad Proteins to Regulate TGFβ Signaling and Cancer Cell Invasion. Cell Commun. Signal 2023, 21, 271. [Google Scholar] [CrossRef] [PubMed]
- Li, Z.; Guo, Y.; Ndandala, C.B.; Chen, H.; Huang, C.; Zhao, G.; Huang, H.; Li, G.; Chen, H. Analysis of circRNA and miRNA Expression Profiles in IGF3-Induced Ovarian Maturation in Spotted Scat (Scatophagus Argus). Front. Endocrinol. 2022, 13, 998207. [Google Scholar] [CrossRef]
- Coen, S.; Keogh, K.; Lonergan, P.; Fair, S.; Kenny, D.A. Early Life Nutrition Affects the Molecular Ontogeny of Testicular Development in the Young Bull Calf. Sci. Rep. 2023, 13, 6748. [Google Scholar] [CrossRef] [PubMed]
T-Cadherin Expression/Key Functional Implications | Tissue/System | Embryonic/Adult | Reference |
---|---|---|---|
Negative guidance cue in the developing nervous system | Migrating neural crest cells and motor neuron axons | Embryogenesis | [4] |
Widespread throughout the CNS (cerebral cortex, medulla, thalamus, hippocampus, and midbrain), in the medulla oblongata, and the nucleus olivaris | Brain and embryonic CNS | Adult and embryogenesis | [20] |
Expression in the heart and large arteries (cardiomyocytes, endothelial cells, VSMCs, and perivascular cells) | Cardiovascular system | Adult | [21] |
Negative guidance cue in physiological angiogenesis; suppresses endothelial cell migration, capillary sprouting, and capillary-like tube formation | Endothelial cells (in vitro, ex vivo, and in vivo models) | Adult | [19] |
Protects endothelial cells from apoptosis under oxidative stress; regulates apoptosis, proliferation, differentiation, migration, and tissue regeneration | Endothelial cells | Adult (stress) | [3,8,9,10] |
Receptor for two metabolically important ligands, adiponectin and LDL, competing for T-cadherin binding | Cardiovascular system | Adult and pathological | [7] |
T-cadherin sequesters adiponectin to cardiac and skeletal muscles and promotes regeneration through binding to T-cadherin | Skeletal muscle | Adult | [12,14,24,25] |
Adiponectin/T-cadherin system enhances exosome biogenesis and secretion, decreasing cellular ceramide levels | Endothelial cells and aorta | Adult | [15] |
T-cadherin expression in the basal layer of keratinocytes is lost upon malignant transformation | Skin (keratinocytes) | Adult and tumors | [23] |
Liver, pancreas, thyroid gland, adrenals, spleen, lymph nodes, stomach, oesophagus, small intestine, gall bladder, bladder, lungs, and bronchi low T-cadherin | Secretory and hemogenic organs and tissues | Adult | [21] |
T-cadherin deficiency leads to spontaneous MSCs adipogenic differentiation and increases their sensitivity to adiponectin-suppressive and LDL-stimulatory effects on adipogenesis | Adipose-derived MSCs | Adult (in vitro) | [17] |
T-cadherin expression rises in atherosclerotic plaques and after arterial injury | Vascular wall | Adult (pathology) | [22] |
T-cadherin/CDH13 loss/silencing correlates with tumor progression | Breast, lung, colorectal, ovarian, endometrial, pancreatic, cervical, nasopharyngeal carcinoma, prostate cancer, retinoblastoma, basal cell carcinoma, cutaneous squamous carcinoma, non-small cell lung carcinoma (NSCLC), gall bladder cancer, and melanoma | Cancer | [3,18,26,27,28,29] |
T-cadherin/CDH13 upregulation correlated with tumor progression | Osteosarcoma, NF1-deficient astrocytoma, and subsets of hepatocellular carcinomas | Cancer | [3,18] |
3 novel forms of soluble T-cadherin | Serum | Type 2 diabetes | [30] |
Age-related bone loss. T-cadherin in plasma inhibits osteoclast differentiation by blocking RANKL signaling | Plasma | Adult (aging) | [31] |
SMC phenotypic modulation by T-cadherin via GSK3β inactivation. Autophagy and survival in VSMCs through MEK1/2/Erk1/2 | Vascular smooth muscle cells | Adult (in vitro) | [32,33] |
CDH13 SNPs association with neuropsychiatric disorders (schizophrenia, ASD, ADHS, alcoholism, and sexual behavior) | Blood, mice models (in vivo) | Adult | [34,35,36,37,38,39,40,41] |
miRNA | ncRNA Type | Interaction with CDH13 | Experimentally Confirmed | Reference |
---|---|---|---|---|
miR-377-3p | miRNA | Direct binding to CDH13 and suppression of its expression | Yes | [99] |
Cluster miR-23a/27a/24-2 | miRNA | Inhibits CDH13 via promoter hypermethylation mediated by suppression of TET1 and activation of DNMT3B | Yes | [119] |
miR-142-5p | miRNA | Activates CDH13 expression by inhibiting hypermethylation through suppression of DNMT1 | Yes | [120] |
miR-101-3p | miRNA | T-cadherin forms a complex with CTRP15 and suppresses miR-101-3p levels, leading to increased ABCA1 expression and cholesterol efflux | Yes | [127] |
miR-675 | miRNA | Direct binding to the 3′-UTR of CDH13, modulating its expression | Yes | [112] |
miR-let7 | miRNA | Direct binding to the 3′-UTR of CDH13, suppressing expression | Yes | [76] |
miR-199b-5p | miRNA | Direct binding and suppression of CDH13 expression | Yes | [87] |
miR-495-3p | miRNA | Predicted bioinformatically to target CDH13 in gastric adenocarcinoma, but not experimentally confirmed | No | [129] |
miR-584-5p | miRNA | Downregulated in cardiac ischemia tissues; predicted to affect CDH13 via bioinformatics, yet not experimentally confirmed | No | [130] |
Group miR-181d, 30a-3p, 30c, 30d, 30e-3p, 370, 493-5p, and 532-5p | miRNA | Predicted to target CDH13; expression profiles in ovarian carcinoma suggest suppression via miRNA direct binding, yet not experimentally confirmed | No | [131] |
miR-2419-5P | miRNA | Inverse correlation between miRNA levels and CDH13 in normal ovarian tissue; binding predicted bioinformatically, not experimentally confirmed | No | [138] |
H19 | lncRNA | Yes | [110,112,113] | |
UPAT | lncRNA | Upregulates UHRF1, leading to epigenetic suppression of CDH13 transcription. | Yes | [122] |
LET1R | lncRNA | Represses CDH13 in lymphatic endothelial cells | Yes | [133] |
LINC00707 | lncRNA | Activates CDH13 expression in keratinocytes following stable suppression of LINC00707. | Yes | [136] |
CDH13-AS2 | lncRNA | Competes with miR-let-7 for binding to the CDH13 mRNA, increasing CDH13 expression | Yes | [76] |
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Rubina, K.; Maier, A.; Klimovich, P.; Sysoeva, V.; Romashin, D.; Semina, E.; Tkachuk, V. T-Cadherin (CDH13) and Non-Coding RNAs: The Crosstalk Between Health and Disease. Int. J. Mol. Sci. 2025, 26, 6127. https://doi.org/10.3390/ijms26136127
Rubina K, Maier A, Klimovich P, Sysoeva V, Romashin D, Semina E, Tkachuk V. T-Cadherin (CDH13) and Non-Coding RNAs: The Crosstalk Between Health and Disease. International Journal of Molecular Sciences. 2025; 26(13):6127. https://doi.org/10.3390/ijms26136127
Chicago/Turabian StyleRubina, Kseniya, Artem Maier, Polina Klimovich, Veronika Sysoeva, Daniil Romashin, Ekaterina Semina, and Vsevolod Tkachuk. 2025. "T-Cadherin (CDH13) and Non-Coding RNAs: The Crosstalk Between Health and Disease" International Journal of Molecular Sciences 26, no. 13: 6127. https://doi.org/10.3390/ijms26136127
APA StyleRubina, K., Maier, A., Klimovich, P., Sysoeva, V., Romashin, D., Semina, E., & Tkachuk, V. (2025). T-Cadherin (CDH13) and Non-Coding RNAs: The Crosstalk Between Health and Disease. International Journal of Molecular Sciences, 26(13), 6127. https://doi.org/10.3390/ijms26136127