Long non-coding RNAs in aging and aging-associated diseases
Long noncoding RNAs (lncRNAs) are a type of RNA, generally defined as transcripts more than 200 nucleotides that are not translated into protein. LncRNAs are roughly classified based on their position relative to protein-coding genes: intergenic (between genes), intragenic/intronic (within genes) and antisense. Until recently, these RNAs were disregarded as “junk”, due to their inability to produce functional proteins. But it is now evident that these lncRNAs can assume crucial roles in almost every aspect of biology. Most annotated lncRNAs are RNA polymerase II (Pol II) transcribed; hence, they are similar in structure to mRNA and may have cap structures and poly A tails. Unlike protein-coding mRNAs, lncRNAs exhibit functional uniqueness by participating in and modulating the various cellular processes such as, histone modification, DNA methylation, and cellular transcription.
Studies have indicated that lncRNAs are involved in epigenetic, transcriptional, post-transcriptional, and translation regulation, as well as post-translational modification.
Cardiovascular diseases (CVDs) are currently the main cause of morbidity and mortality. It was found that 145 lncRNAs are differentially expressed in ischemic cardiomyopathy tissues compared with healthy control samples. Thus, overcoming the challenges of determining cardiac-related lncRNAs and their molecular mechanisms may be significantly beneficial to our further investigations in the diagnosis and treatment of CVDs. However, treatment strategies on targeting lncRNA remain difficult to apply to the clinic.  
The endothelial cells that line the vessel walls play an important role in the development of atherosclerosis. Non-coding RNA such as long non-coding RNAs are known to play an important role in endothelial function and are implicated in the disease progression. Of 4465 lncRNAs expressed in the human endothelium, 798 lncRNAs are dysregulated in advanced age. Among these differentially expressed lncRNAs, prostate-cancer-associated transcript 14 (PCAT14), which is localized in the nucleus of young endothelial cells, but significantly reduced in aged endothelium. By silencing PCAT14, it was demonstrated that endothelial cell migration and sprouting capacity were reduced, without affecting the endothelial proliferative capacity. Furthermore, silencing of PCAT14 resulted in increased expression of inflammatory genes (e.g., ICAM1 and SELE) and genes relevant to endothelial cell stalk formation (e.g., JAG1 and ESM1), suggesting that PCAT14 may be important in maintaining the healthy status of the endothelium.
lncRNA participates in multiple aging-related neurological disorders development. Accumulating evidence has implicated lncRNA dysregulation in neurodegenerative disorders, including Alzheimer’s disease, whereby a group of long non-coding RNAs in blood can serve as a specific biomarker of Alzheimer's disease Parkinson’s disease, and Huntington’s disease (Tan et al., 2021)
Long non-coding RNAs and rheumatoid arthritis
Various lncRNAs have proven potential as biomarkers and targets for diagnosing, prognosis and treating rheumatoid arthritis.
Accumulating evidence revealed that the regulatory network that includes long non-coding RNAs (lncRNAs)/circular RNAs (circRNAs), micro RNAs (miRNAs), and messenger RNAs (mRNA) plays important roles in regulating the pathological and physiological processes in rheumatoid arthritis. lncRNAs/circRNAs act as the miRNA sponge and competitively bind to miRNA to regulate the expression mRNA in synovial tissue, fibroblast-like synoviocytes (FLS), and peripheral blood mononuclear cells (PBMCs), participate in the regulation of proliferation, apoptosis, invasion, and inflammatory response.
Role of the lncRNA–miRNA–mRNA Axis in Chronic Inflammatory Airway Diseases
 Emerging evidence suggests that lncRNAs account for the regulation of macrophage polarization and subsequent effects on respiratory diseases.
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- ↑ Palazzo, A. F., & Koonin, E. V. (2020). Functional long non-coding RNAs evolve from junk transcripts. Cell, 183(5), 1151-1161. PMID: 33068526 DOI: 10.1016/j.cell.2020.09.047
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- ↑ Statello, L., Guo, C. J., Chen, L. L., & Huarte, M. (2021). Gene regulation by long non-coding RNAs and its biological functions. Nature reviews Molecular cell biology, 22(2), 96-118. PMID: 33353982 PMCID: PMC7754182 DOI: 10.1038/s41580-020-00315-9
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- ↑ Nie, X., Fan, J., & Wang, D. W. (2023). The Function and Therapeutic Potential of lncRNAs in Cardiac Fibrosis. Biology, 12(2), 154. PMID: 36829433 PMCID: PMC9952806 DOI: 10.3390/biology12020154
- ↑ Lozano-Vidal, N., Bink, D. I., & Boon, R. A. (2019). Long noncoding RNA in cardiac aging and disease. Journal of molecular cell biology, 11(10), 860-867. PMID: 31152659 PMCID: PMC6884711 DOI: 10.1093/jmcb/mjz046
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- ↑ Bhattacharya, M., Sharma, A. R., & Chakraborty, C. (2022). Challenges of Long Non Coding RNAs in Human Disease Diagnosis and Therapies: Bio-Computational Approaches. In Handbook of Machine Learning Applications for Genomics (pp. 121-131). Singapore: Springer Nature Singapore. https://doi.org/10.1007/978-981-16-9158-4_8
- ↑ Bink, D. I., Pauli, J., Maegdefessel, L., & Boon, R. A. (2023). Endothelial microRNAs and long noncoding RNAs in cardiovascular ageing. Atherosclerosis. S0021-9150(23)00136-3 PMID: 37059656 DOI: 10.1016/j.atherosclerosis.2023.03.019
- ↑ Drekolia, M. K., Talyan, S., Cordellini Emidia, R., Boon, R. A., Guenther, S., Looso, M., ... & Bibli, S. I. (2022). Unravelling the impact of aging on the human endothelial lncRNA transcriptome. bioRxiv, 2022-09. PMID: 36338971 PMCID: PMC9634578 DOI: 10.3389/fgene.2022.1035380
- ↑ Ni, Y. Q., Xu, H., & Liu, Y. S. (2022). Roles of long non-coding RNAs in the development of aging-related neurodegenerative diseases. Frontiers in Molecular Neuroscience, 15. PMID: 35359573 PMCID: PMC8964039 DOI: 10.3389/fnmol.2022.844193
- ↑ Ren, Z., Chu, C., Pang, Y., Cai, H., & Jia, L. (2023). A Group of Long Non-coding RNAs in Blood Acts as a Specific Biomarker of Alzheimer’s Disease. Molecular Neurobiology, 60(2), 566-575. PMID: 36327022 DOI: 10.1007/s12035-022-03105-w
- ↑ Canseco-Rodriguez, A., Masola, V., Aliperti, V., Meseguer-Beltran, M., Donizetti, A., & Sanchez-Perez, A. M. (2022). Long Non-Coding RNAs, Extracellular Vesicles and Inflammation in Alzheimer’s Disease. International Journal of Molecular Sciences, 23(21), 13171. PMID: 36361952 PMCID: PMC9654199 DOI: 10.3390/ijms232113171
- ↑ Sivagurunathan, N., Ambatt, A. T., & Calivarathan, L. (2022). Role of Long Non-coding RNAs in the Pathogenesis of Alzheimer’s and Parkinson’s Diseases. Current Aging Science, 15(2), 84-96. PMID: 35081899 DOI: 10.2174/1874609815666220126095847
- ↑ Na, C., Wen-Wen, C., Li, W., Ao-Jia, Z., & Ting, W. (2022). Significant Role of Long Non-coding RNAs in Parkinson’s Disease. Current Pharmaceutical Design, 28(37), 3085-3094. PMID: 36154598 DOI: 10.2174/1381612828666220922110551
- ↑ Elazazy, O., Midan, H. M., Shahin, R. K., Elesawy, A. E., Elballal, M. S., Sallam, A. A. M., ... & Doghish, A. S. (2023). Long non-coding RNAs and rheumatoid arthritis: Pathogenesis and clinical implications. Pathology-Research and Practice, 154512. PMID: 37172525 DOI: 10.1016/j.prp.2023.154512
- ↑ Han, J. J., Wang, X. Q., & Zhang, X. A. (2022). Functional interactions between lncRNAs/circRNAs and miRNAs: Insights into rheumatoid arthritis. Frontiers in Immunology, 13, 810317. PMID: 35197980 PMCID: PMC8858953 DOI: 10.3389/fimmu.2022.810317
- ↑ Qiao, X., Hou, G., He, Y. L., Song, D. F., An, Y., Altawil, A., ... & Yin, Y. (2022). The Novel Regulatory Role of the lncRNA–miRNA–mRNA Axis in Chronic Inflammatory Airway Diseases. Frontiers in Molecular Biosciences, 605. PMID: 35769905 PMCID: PMC9234692 DOI: 10.3389/fmolb.2022.927549
- ↑ Qiao, X., Ding, Y., Wu, D., Zhang, A., Yin, Y., Wang, Q., ... & Kang, J. (2022). The roles of long noncoding RNA-mediated macrophage polarization in respiratory diseases. Frontiers in Immunology, 13. PMID: 36685535 PMCID: PMC9849253 DOI: 10.3389/fimmu.2022.1110774
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