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REVIEW ARTICLE

Current insights and advances in long noncoding RNA dysregulation in diabetes and its complications

Ali Afzal1† ,  Huma Rasheed2† ,  Shaaf Ahmad3† ,  Sadia Ahmad1,4† ,  Faiqa Irshad2† ,  Mehreen Iftikhar2 ,  Muhammad Imran5 ,  Zaman Gul4 ,  Umair Ali Khan Saddozai6 ,  Xinying Ji7,8* ,  Muhammad Babar Khawar2,6*
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1 Department of Zoology, Faculty of Sciences and Technology, University of Central Punjab, Lahore, Punjab, Pakistan
2 Department of Zoology, University of Narowal, Narowal, Punjab, Pakistan
3 King Edward Medical University/Mayo Hospital, Lahore, Punjab, Pakistan
4 Institute of Zoology, University of Punjab, Lahore, Punjab, Pakistan
5 Center of Applied Molecular Biology, University of the Punjab, Lahore, Punjab, Pakistan
6 Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China
7 Faculty of Basic Medical Subjects, Shu-Qing Medical College of Zhengzhou, Zhengzhou, Jiangsu, China
8 Department of Medicine, Huaxian County People’s People’s Hospital, Huaxian Henan Province, China
GPD, 4000 https://doi.org/10.36922/gpd.4000
Submitted: 20 June 2024 | Accepted: 23 September 2024 | Published: 10 December 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Long noncoding RNAs (lncRNAs) are pivotal regulators in the pathophysiology of diabetes mellitus and its complications, including diabetic retinopathy, nephropathy, and cardiomyopathy. They influence essential cellular processes such as angiogenesis, vascular smooth muscle cell behavior, inflammation, extracellular matrix remodeling, and apoptosis. In cardiomyopathy, lncRNA H19 promotes cardiomyocyte survival by regulating autophagy, highlighting its role in cardiovascular outcomes. In addition, lncRNAs hold promise as noninvasive biomarkers, detectable in extracellular fluids such as serum and urine, providing novel diagnostic tools. For example, elevated levels of HOX transcript antisense RNA and promoter of CDKN1A antisense DNA damage-activated RNA correlate with hyperglycemia and its complications, whereas maternally expressed gene 3 and metastasis-associated lung adenocarcinoma transcript 1 are linked to insulin resistance. However, the full scope of lncRNA mechanisms and therapeutic potential remains unclear. Recent research emphasizes the importance of studying the molecular pathways influenced by lncRNAs, such as the Janus kinase/signal transducer and activator of transcription and p38 mitogen-activated protein kinase pathways, which regulate inflammation and insulin signaling. Preclinical studies show promising outcomes for lncRNA-targeted therapies; however, challenges remain in precise detection and delivery. Addressing these gaps through advanced RNA sequencing and targeted therapies is crucial for developing lncRNA-based diagnostics and treatments for diabetes complications. This review explores lncRNAs as biomarkers and therapeutic targets, focusing on their regulatory mechanisms in diabetic complications such as retinopathy, nephropathy, and cardiomyopathy.

Keywords
Diabetes mellitus
Long noncoding RNA
Biomarkers
Transcriptional control
Insulin resistance
Vascular problems
Funding
None.
Conflict of interest
Umair Ali Khan Saddozai and Xinying Ji are the Editorial Board Members of this journal but were not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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Gene & Protein in Disease, Electronic ISSN: 2811-003X Published by AccScience Publishing
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