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Li GZ, Liu JY, Zhou H. Ferroptosis: A novel therapeutic target for diabetic cardiomyopathy. World J Diabetes 2025; 16:104665. [DOI: 10.4239/wjd.v16.i6.104665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 03/24/2025] [Accepted: 05/07/2025] [Indexed: 06/13/2025] Open
Abstract
Ferroptosis is a new type of programmed cell death caused by the accumulation of iron-dependent lipid peroxides, and it plays a role in the occurrence and progression of diverse diseases. Diabetic cardiomyopathy (DCM), a serious cardiovascular complication in patients with diabetes, eventually progresses to refractory heart failure (HF), which increases the risk of hospitalization for HF and cardiovascular death in patients with diabetes. Despite glycemic control, effective strategies to prevent DCM onset are currently lacking. Accumulating evidence suggests that ferroptosis is involved in oxidative stress, inflammation, and abnormal autophagy in diabetic myocardium, which plays an important role in myocardial apoptosis, hypertrophy, and cardiac fibrosis. The inhibition of ferroptosis can relieve DCM. Presently, ferroptosis inhibitors have been broadly suggested for the treatment of iron overload-related cardiomyopathy. This article reviewed relevant studies to offer a new therapeutic target for DCM.
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Affiliation(s)
- Gui-Zhi Li
- Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Jia-Yin Liu
- Department of Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
| | - Hong Zhou
- Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
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Tian M, Cao J, Li M, Lou P, Ma H, Liu Y, Li Y. Associations of circulating omentin-1 levels and long noncoding RNA MALAT1 expression with coronary heart disease in patients with type 2 diabetes mellitus. Sci Rep 2025; 15:16376. [PMID: 40350526 PMCID: PMC12066706 DOI: 10.1038/s41598-025-01153-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 05/05/2025] [Indexed: 05/14/2025] Open
Abstract
Coronary heart disease (CHD) is a severe diabetic vascular complication and the main cause of mortality among diabetes patients. Early diagnosis of CHD could prevent its development. Both omentin-1 (Oment-1) and the long noncoding RNA MALAT1 (lncRNA MALAT1) can be detected in peripheral blood and exhibit protective or detrimental effects on CHD. However, whether these two factors could be predictive of CHD in T2DM patients remains unclear. Therefore, this study aimed to investigate the associations of circulating Oment-1 levels and the expression of MALAT1 with CHD in T2DM patients and to assess their predictive efficacy. A total of 137 T2DM patients were enrolled, including 68 patients without CHD (T2DM group) and 69 patients with CHD (T2DM + CHD group). Clinical parameters were collected, and plasma Oment-1 was measured by enzyme-linked immunosorbent assay (ELISA). RNA was isolated from peripheral monocytes, and the expression of MALAT1 was determined by quantitative PCR. Cardiac function was measured by echocardiography. Compared with that in T2DM patients, the plasma Oment-1 level was significantly lower, while the expression of MALAT1 was significantly greater in T2DM + CHD patients (all P values < 0.01). Bivariate correlation analysis indicated that Oment-1 was positively correlated with the left ventricular ejection fraction (LVEF) (P < 0.01). MALAT1 expression was negatively correlated with LVEF but positively correlated with age and DM duration (P < 0.05). Binary logistic regression suggested that Oment-1 and MALAT1 were significantly associated with the presence of CHD. Receiver operating characteristic (ROC) curve analysis demonstrated that both Oment-1 (AUC = 0.663, sensitivity = 75%, specificity = 49%) and MALAT1 (AUC = 0.749, sensitivity = 73%, specificity = 66%) had significant diagnostic value for CHD among T2DM patients. Notably, the combination of Oment-1 and MALAT1 exhibited better diagnostic efficiency (AUC = 0.771, sensitivity = 66.7%, specificity = 75.3%). In conclusion, decreased circulating Oment-1 levels and increased MALAT1 expression are closely associated with CHD in T2DM patients, and their combination offers superior diagnostic efficiency, suggesting Oment-1 and MALAT1 may serve as a non-invasive tool for the early CHD detection and risk stratification in high-risk T2DM patients. Further studies are warranted to explore the pathophysiological mechanisms of Omentin-1 and MALAT1 in the pathogenesis of CHD in T2DM and to validate their clinical utility as potential biomarkers in large cohort studies.
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Affiliation(s)
- Meimei Tian
- Department of Endocrinology, The Third Hospital of Hebei Medical University, Ziqiang Road 139, Shijiazhuang City, 050051, Hebei Province, China
| | - Jinchao Cao
- Department of Pediatric Orthopedics, The Third Hospital of Hebei Medical University, Ziqiang Road 139, Shijiazhuang City, 050051, Hebei Province, China
| | - Min Li
- Department of Endocrinology, The Third Hospital of Hebei Medical University, Ziqiang Road 139, Shijiazhuang City, 050051, Hebei Province, China
| | - Pingping Lou
- Department of Endocrinology, The Third Hospital of Hebei Medical University, Ziqiang Road 139, Shijiazhuang City, 050051, Hebei Province, China
| | - Huijie Ma
- Department of Physiology, Hebei Medical University, Zhongshan East Road 361, Shijiazhuang City, Hebei Province, China
- Hebei Collaborative Innovation Center for Cardio- Cerebrovascular Disease, Shijiazhuang, 050051, China
| | - Yan Liu
- Department of Endocrinology, The Third Hospital of Hebei Medical University, Ziqiang Road 139, Shijiazhuang City, 050051, Hebei Province, China.
- Department of Endocrinology, The Third Hospital of Hebei Medical University, Ziqiang Road 139, Shijiazhuang City, 050051, Hebei Province, China.
| | - Yukun Li
- Department of Endocrinology, The Third Hospital of Hebei Medical University, Ziqiang Road 139, Shijiazhuang City, 050051, Hebei Province, China.
- Department of Endocrinology, The Third Hospital of Hebei Medical University, Ziqiang Road 139, Shijiazhuang City, 050051, Hebei Province, China.
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Rattanapan Y, Duangchan T, Sai-ong T, Chareonsirisuthigul T. miR-4428 and miR-185-5p as Key Modulators of Insulin Sensitivity and Glucose Homeostasis: Insights into Pathways and Therapeutic Potential in Type 2 Diabetes Mellitus. BIOLOGY 2025; 14:424. [PMID: 40282289 PMCID: PMC12025167 DOI: 10.3390/biology14040424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2025] [Revised: 04/03/2025] [Accepted: 04/07/2025] [Indexed: 04/29/2025]
Abstract
Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and dysregulation of glucose metabolism. MicroRNAs (miRNAs) such as miR-4428 and miR-185-5p play critical roles in post-transcriptional regulation of genes involved in these processes, but their specific contributions to T2DM pathogenesis remain unclear. Plasma samples from T2DM patients and non-diabetic controls were analyzed for miR-4428 and miR-185-5p expression using microarray and bioinformatics tools. Target genes were predicted, and pathway enrichment analysis was performed to explore biological roles. Differential expression analysis revealed a 2.3-fold upregulation of miR-4428 and a 14.4-fold downregulation of miR-185-5p in T2DM patients compared to controls. Predicted targets such as ADAR, KLF9, and SOGA1 were linked to glucose metabolism and insulin signaling pathways. Enrichment analysis highlighted associations with neuronal signaling, chromatin remodeling, and metabolic regulation pathways. miR-4428 and miR-185-5p regulate critical insulin sensitivity and glucose metabolism pathways, making them promising biomarkers and therapeutic targets for managing T2DM. Future studies should validate these findings experimentally to advance miRNA-based interventions for T2DM and its complications.
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Affiliation(s)
- Yanisa Rattanapan
- Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand; (Y.R.); (T.D.)
- Hematology and Transfusion Science Research Center, Walailak University, Nakhon Si Thammarat 80160, Thailand
| | - Thitinat Duangchan
- Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand; (Y.R.); (T.D.)
- Hematology and Transfusion Science Research Center, Walailak University, Nakhon Si Thammarat 80160, Thailand
| | - Thaveesak Sai-ong
- School of Public Health, Walailak University, Nakhon Si Thammarat 80160, Thailand;
| | - Takol Chareonsirisuthigul
- Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
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Han G, Hu K, Luo T, Wang W, Zhang D, Ouyang L, Liu X, Liu J, Wu Y, Liang J, Ling J, Chen Y, Xuan R, Zhang J, Yu P. Research progress of non-coding RNA regulating the role of PANoptosis in diabetes mellitus and its complications. Apoptosis 2025; 30:516-536. [PMID: 39755822 DOI: 10.1007/s10495-024-02066-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2024] [Indexed: 01/06/2025]
Abstract
Diabetes is a chronic metabolic disease that is endemic worldwide and is characterized by persistent hyperglycemia accompanied by multiple severe complications, including cardiovascular disease, kidney dysfunction, neuropathy, and retinopathy. The pathogenesis of diabetes mellitus and its complications is multifactorial, involving various molecular and cellular pathways. In recent years, research has indicated that mechanisms of cell death play a significant role in the advancement of diabetes and its complications. PANoptosis is a complex phenomenon caused by three cell death pathways: programmed apoptosis, necroptosis and pyroptosis. The contribution of PANoptosis to diabetes and its complications remains incompletely understood. Non-coding RNA, an important molecule in gene expression regulation, has shown significant regulatory functions in a variety of diseases. This paper reviews the underlying mechanisms of diverse types of non-coding RNAs (including lncRNA, miRNA and circRNA) in regulating PANoptosis and their specific contributions in diabetes, aiming to explore how non-coding RNAs influence PANoptosis and their effects in diabetes.
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Affiliation(s)
- Guangyu Han
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China
- The Second Clinical Medical College, Nanchang University, Nanchang, 330006, China
| | - Kaibo Hu
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China
- The Second Clinical Medical College, Nanchang University, Nanchang, 330006, China
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Tianfeng Luo
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China
- The Second Clinical Medical College, Nanchang University, Nanchang, 330006, China
| | - Wenting Wang
- Department of Anesthesiology, The Second Affiliated Hospital of Hainan Medical University, Haikou, 571199, China
| | - Deju Zhang
- Ood and Nutritional Sciences, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, China
| | - Liu Ouyang
- Center for Molecular and Translational Medicine, Georgia State University, 157 Decatur Street SE, Atlanta, GA, 30303, USA
| | - Xiao Liu
- Department of Cardiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Jianping Liu
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China
| | - Yuting Wu
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China
| | - Jianqi Liang
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China
| | - Jitao Ling
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China
| | - Yixuan Chen
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China
| | - Rui Xuan
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
| | - Jing Zhang
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
| | - Peng Yu
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
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Alabere HO, Taylor AD, Miller BR, Nohoesu R, Nicoletti R, Mogus J, Meadows EM, Hollander JM. Noncoding RNA as potential therapeutics to rescue mitochondrial dysfunction in cardiovascular diseases. Am J Physiol Heart Circ Physiol 2025; 328:H846-H864. [PMID: 40019197 DOI: 10.1152/ajpheart.00774.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 12/16/2024] [Accepted: 02/25/2025] [Indexed: 03/01/2025]
Abstract
Noncoding RNAs (ncRNAs) are critical regulators of mitochondrial function in cardiovascular diseases. Several studies have explored the manipulation of ncRNAs in mitochondrial dysfunction in different cardiovascular disease contexts, however, there is a dearth of information on the exploration of these noncoding RNAs as actual therapeutics to ameliorate cardiovascular diseases. This systematic review examines the roles of various ncRNAs in modulating mitochondrial dysfunction across major cardiovascular diseases and how they can be targeted to the mitochondria. A comprehensive literature search was conducted using Web of Science and Scopus databases, following the PRISMA guidelines. Original research articles in the English language, focusing on ncRNAs and mitochondrial dysfunction in specific cardiovascular diseases, were eligible for inclusion. A total of 76 studies were included in the systematic review with up to 100 ncRNAs identified as therapeutic biomarkers. The identified ncRNAs participate in regulating mitochondrial processes including oxidative phosphorylation (OXPHOS), fission/fusion dynamics, apoptosis, and calcium handling in cardiovascular diseases. Mitochondrial targeting moieties including mitochondrial targeting cell-penetrating peptides, mitochondrial targeting liposomes, and aptamers can be conjugated to ncRNAs and delivered to the heart via various injection routes including the pericardium or the myocardium. However, significant challenges remain in developing effective delivery methods to modulate these ncRNAs in vivo.
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Affiliation(s)
- Hafsat O Alabere
- Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia, United States
- Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, West Virginia, United States
| | - Andrew D Taylor
- Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia, United States
- Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, West Virginia, United States
| | - Brianna R Miller
- Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, West Virginia, United States
- Department of Biochemistry and Molecular Medicine, West Virginia University School of Medicine, Morgantown, West Virginia, United States
| | - Remi Nohoesu
- Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia, United States
- Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, West Virginia, United States
| | - Roxy Nicoletti
- Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia, United States
| | - Joshua Mogus
- Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, West Virginia, United States
- Department of Physiology, Pharmacology and Toxicology, West Virginia University School of Medicine, Morgantown, West Virginia, United States
| | - Ethan M Meadows
- Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, West Virginia, United States
| | - John M Hollander
- Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, West Virginia, United States
- Department of Physiology, Pharmacology and Toxicology, West Virginia University School of Medicine, Morgantown, West Virginia, United States
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Liu Y, Yuan J, Zhang Y, Ma T, Ji Q, Tian S, Liu C. Non-coding RNA as a key regulator and novel target of apoptosis in diabetic cardiomyopathy: Current status and future prospects. Cell Signal 2025; 128:111632. [PMID: 39922440 DOI: 10.1016/j.cellsig.2025.111632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 01/19/2025] [Accepted: 01/27/2025] [Indexed: 02/10/2025]
Abstract
The occurrence of diabetic cardiomyopathy (DCM) can be independent of several risk factors such as hypertension and myocardial ischemia, which can lead to heart failure, thus seriously threatening human health and life. Sustained hyperglycemic stimulation can induce cardiomyocyte apoptosis, which is recognized as the pathological basis of DCM. It has been demonstrated that dysregulation induced by apoptosis is closely associated to progression of DCM, but mechanisms behind it requires further clarification. Currently, increasing evidence has shown that non-coding RNA (ncRNA), especially microRNA, long-chain non-coding RNA (lncRNA), and circular RNA (circRNA), play a regulative role in apoptosis, thus affecting the progression of DCM. Notably, some ncRNAs have also exhibit potential significance as biomarkers and/or therapeutic targets for patients with DCM. In this review, recent findings regarding the potential mechanisms of ncRNA in regulating apoptosis and their role in the progression of DCM were systematically summarized in this research. The conclusion reveals that ncRNA abnormalities exert a crucial role in pathological changes of DCM, which offers potential therapeutic targets for the prevention of DCM.
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Affiliation(s)
- Yicheng Liu
- College of Rehabilitation Medicine,Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Jie Yuan
- Science and Technology Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China
| | - Yuhang Zhang
- College of Rehabilitation Medicine,Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Ting Ma
- College of Rehabilitation Medicine,Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Qianqian Ji
- Department one of Cardiovascular Disease, Tai'an Hospital of Traditional Chinese Medicine, Taian 271000, China
| | - Sheng Tian
- Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao 999078, PR China; Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Chunxiao Liu
- Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan 250012, China.
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Shaheen N, Zhao J. Emerging Role of CircularRNA-Cacna1d in Sepsis-induced Lung Injury: A Potential Therapeutic Target and Biomarker. Am J Respir Cell Mol Biol 2025; 72:122-123. [PMID: 39288398 PMCID: PMC11976653 DOI: 10.1165/rcmb.2024-0424ed] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 09/17/2024] [Indexed: 09/19/2024] Open
Affiliation(s)
- Nargis Shaheen
- Department of Physiology and Cell Biology Davis Heart and Lung Research Institute The Ohio State University College of Medicine Columbus, Ohio
| | - Jing Zhao
- Department of Physiology and Cell Biology Davis Heart and Lung Research Institute The Ohio State University College of Medicine Columbus, Ohio
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Cao Q, Dong Z, Xi Y, Zhong J, Huang J, Yang Q. Construction of a potentially functional long noncoding RNA-microRNA-mRNA network in diabetic cardiomyopathy. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2024; 29:74. [PMID: 39871870 PMCID: PMC11771823 DOI: 10.4103/jrms.jrms_205_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 08/02/2024] [Accepted: 09/20/2024] [Indexed: 01/29/2025]
Abstract
Background Diabetic cardiomyopathy (DCM) is a severe complication among patients with Type 2 diabetes, significantly increasing heart failure risk and mortality. Despite various implicated mechanisms, effective DCM treatments remain elusive. This study aimed to construct a comprehensive competing endogenous RNA (ceRNA) network in DCM using bioinformatics analysis. Materials and Methods Three expression profiles datasets (GSE161827, GSE161931, and GSE241166) were collected from gene expression omnibus database and then integrated for the identification of differentially expressed genes (DEGs). Gene Ontology, Kyoto Encyclopedia of Gene and Genome pathway analysis, and Gene set enrichment analysis (GSEA) were employed for functional analysis. Protein-protein interaction (PPI) network and hub genes were also identified. The ceRNA regulatory networks were constructed based on interaction between long noncoding RNA (lncRNA) and DEGs, microRNA (miRNA) and DEGs, as predicted by public available databases. Results A total of 105 DEGs, including 44 upregulated and 61 downregulated genes were identified to be associated with DCM. Functional enrichment analysis showed that fatty acid metabolism pathway and inflammatory responses were significantly enriched in DCM. A total of 56 interactions between miRNA with DEGs, and 27 interactions between lncRNA with miRNA was predicted. Besides, a ceRNA network includes 9 mRNA, 17 miRNA and 10 lncRNA was constructed, among which Cdh20 and Cacna2d2 were hub genes in PPI network. Conclusion The identified hub genes and ceRNA network components provide valuable insights into DCM biology and offer potential diagnostic biomarkers and therapeutic targets for further investigation. Further experimental validation and clinical studies are warranted to translate these findings into clinical applications.
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Affiliation(s)
- Qiwen Cao
- Department of Endocrinology, Bin Hai Wan Central Hospital of Dongguan, Dongguan, China
| | - Zhihui Dong
- Department of Cardiology, Bin Hai Wan Central Hospital of Dongguan, Dongguan, China
| | - Yangbo Xi
- Department of Cardiology, Bin Hai Wan Central Hospital of Dongguan, Dongguan, China
| | - Jiana Zhong
- Department of Endocrinology, Bin Hai Wan Central Hospital of Dongguan, Dongguan, China
| | - Jianzhong Huang
- Central Laboratory, Bin Hai Wan Central Hospital of Dongguan, Dongguan, China
| | - Qunfeng Yang
- Department of Endocrinology, Bin Hai Wan Central Hospital of Dongguan, Dongguan, China
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Taylor AD, Hathaway QA, Meadows EM, Durr AJ, Kunovac A, Pinti MV, Cook CC, Miller BR, Nohoesu R, Nicoletti R, Alabere HO, Robart AR, Hollander JM. Diabetes mellitus disrupts lncRNA Malat1 regulation of cardiac mitochondrial genome-encoded protein expression. Am J Physiol Heart Circ Physiol 2024; 327:H1503-H1518. [PMID: 39453425 PMCID: PMC11684948 DOI: 10.1152/ajpheart.00607.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 10/09/2024] [Accepted: 10/21/2024] [Indexed: 10/26/2024]
Abstract
Understanding the cellular mechanisms behind diabetes-related cardiomyopathy is crucial as it is a common and deadly complication of diabetes mellitus. Dysregulation of the mitochondrial genome has been linked to diabetic cardiomyopathy and can be ameliorated by altering microRNA (miRNA) availability in the mitochondrion. Long noncoding RNAs (lncRNAs) have been identified to downregulate miRNAs. This study aimed to determine if diabetes mellitus impacts the mitochondrial localization of lncRNAs, their interaction with miRNAs, and how this influences mitochondrial and cardiac function. In mouse and human nondiabetic and type 2 diabetic cardiac tissue, RNA was isolated from purified mitochondria and sequenced (Ilumina HiSeq). Malat1 was significantly downregulated in both human and mouse cardiac mitochondria. The use of a mouse model with an insertional deletion of Malat1 transcript expression resulted in exacerbated systolic and diastolic dysfunction when evaluated in conjunction with a high-fat diet. The cardiac effects of a high-fat diet were countered in a mouse model with transgenic overexpression of Malat1. MiR-320a, a miRNA that binds to both mitochondrial genome-encoded gene NADH-ubiquinone oxidoreductase chain 1 (MT-ND1) as well as Malat1, was upregulated in human and mouse diabetic mitochondria. Conversely, MT-ND1 was downregulated in human and mouse diabetic mitochondria. Mice with an insertional inactivation of Malat1 displayed increased recruitment of both miR-320a and MT-ND1 to the RNA-induced silencing complex (RISC). In vitro pulldown assays of Malat1 fragments with conserved secondary structure confirmed binding capacity for miR-320a. In vitro Seahorse assays indicated that Malat1 knockdown and miR-320a overexpression impaired overall mitochondrial bioenergetics and Complex I functionality. In summary, the disruption of Malat1 presence in mitochondria, as observed in diabetic cardiomyopathy, is linked to cardiac dysfunction and mitochondrial genome regulation.NEW & NOTEWORTHY Currently, there is no known mechanism for the development of diabetes-related cardiac dysfunction. Previous evaluations have shown that mitochondria, specifically mitochondrial genome-encoded transcripts, are disrupted in diabetic cardiac cells. This study explores the presence of long noncoding RNAs (lncRNAs) such as Malat1 in cardiac mitochondria and how that presence is impacted by diabetes mellitus. Furthermore, this study will examine how the loss of Malat1 results in bioenergetic and cardiac dysfunction through mitochondrial transcriptome dysregulation.
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MESH Headings
- RNA, Long Noncoding/genetics
- RNA, Long Noncoding/metabolism
- Animals
- Humans
- Mitochondria, Heart/metabolism
- Mitochondria, Heart/genetics
- MicroRNAs/genetics
- MicroRNAs/metabolism
- Diabetic Cardiomyopathies/genetics
- Diabetic Cardiomyopathies/metabolism
- Diabetic Cardiomyopathies/physiopathology
- Diabetic Cardiomyopathies/etiology
- Male
- Mice
- Mice, Inbred C57BL
- Diabetes Mellitus, Type 2/genetics
- Diabetes Mellitus, Type 2/metabolism
- Genome, Mitochondrial/genetics
- Gene Expression Regulation
- Mitochondrial Proteins/genetics
- Mitochondrial Proteins/metabolism
- Myocytes, Cardiac/metabolism
- Myocytes, Cardiac/pathology
- Diet, High-Fat
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Affiliation(s)
- Andrew D Taylor
- Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia, United States
- Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, West Virginia, United States
| | - Quincy A Hathaway
- Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia, United States
- Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
| | - Ethan M Meadows
- Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, West Virginia, United States
| | - Andrya J Durr
- Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia, United States
- Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, West Virginia, United States
| | - Amina Kunovac
- Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia, United States
- Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, West Virginia, United States
| | - Mark V Pinti
- Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, West Virginia, United States
| | - Chris C Cook
- Cardiovascular and Thoracic Surgery, West Virginia University School of Medicine, Morgantown, West Virginia, United States
| | - Brianna R Miller
- Department of Biochemistry, West Virginia University School of Medicine, Morgantown, West Virginia, United States
| | - Remi Nohoesu
- Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia, United States
- Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, West Virginia, United States
| | - Roxy Nicoletti
- Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia, United States
| | - Hafsat O Alabere
- Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia, United States
- Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, West Virginia, United States
| | - Aaron R Robart
- Department of Biochemistry, West Virginia University School of Medicine, Morgantown, West Virginia, United States
| | - John M Hollander
- Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia, United States
- Mitochondria, Metabolism & Bioenergetics Working Group, West Virginia University School of Medicine, Morgantown, West Virginia, United States
- Department of Physiology, West Virginia University School of Medicine, Morgantown, West Virginia, United States
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Aihemaiti G, Song N, Luo J, Liu F, Toyizibai J, Adili N, Liu C, Ji W, Yang YN, Li X. Targeting lncRNA MALAT1: A Promising Approach to Overcome Metabolic Syndrome. Int J Endocrinol 2024; 2024:1821252. [PMID: 39502508 PMCID: PMC11535177 DOI: 10.1155/2024/1821252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 08/20/2024] [Accepted: 10/08/2024] [Indexed: 11/08/2024] Open
Abstract
Metabolic syndrome (MetS) is a collection of metabolic abnormalities including insulin resistance, atherogenic dyslipidemia, central obesity, and hypertension. Recently, long noncoding RNAs (lncRNAs) have emerged as pivotal regulators of metabolic balance, influencing the genes associated with MetS. Although the prevalence of insulin resistance is rising, leading to an increased risk of type 2 diabetes mellitus (T2DM) and its vascular complications, there is still a notable gap in understanding the role of lncRNAs in the context of clinical diabetes. Among lncRNAs, lung adenocarcinoma metastasis-associated transcript 1 (MALAT1) has been identified as a significant regulator of metabolism-related disorders, including T2DM and cardiovascular disease (CVD). This review explores the mechanism of lncRNA MALAT1 and suggests that targeting it could offer a promising strategy to combat MetS, thereby enhancing the prognosis of MetS.
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Affiliation(s)
- Gulandanmu Aihemaiti
- Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Ning Song
- Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Junyi Luo
- Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Fen Liu
- Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
- Xinjiang Key Laboratory of Cardiovascular Disease Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Jianaerguli Toyizibai
- Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Niyaziaili Adili
- Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Chang Liu
- Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Wei Ji
- Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Yi-Ning Yang
- Xinjiang Key Laboratory of Cardiovascular Disease Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
- People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Xiaomei Li
- Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
- Xinjiang Key Laboratory of Cardiovascular Disease Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
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Yang C, Fan H, Wu Y, Liang Z, Wang Y, Wu A, Li Y, Yuan Z, Yi J, Yin D, Wu J. T-2 toxin exposure induces ovarian damage in sows: lncRNA CUFF.253988.1 promotes cell apoptosis by inhibiting the SIRT3/PGC1α pathway. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 283:116787. [PMID: 39067079 DOI: 10.1016/j.ecoenv.2024.116787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 07/17/2024] [Accepted: 07/24/2024] [Indexed: 07/30/2024]
Abstract
T-2 toxin, a mycotoxin found in foods and feeds, poses a threat to female reproductive health in both humans and animals. LncRNA CUFF.253988.1 (CUFF.253988.1), highly expressed in pigs, has an undisclosed regulatory role. This study aimed to establish a model of T-2 toxin-induced ovarian injury in sows, both in vivo and in vitro, and to explore the regulatory role and potential mechanisms of CUFF.253988.1. The results showed that feeding T-2 toxin-contaminated feed (1 mg/kg) induced ovarian follicle atresia and mitochondrial structural damage, accompanied by a significant upregulation of CUFF.253988.1 expression in the ovaries. Additionally, T-2 toxin inhibited the SIRT3/PGC1-α pathway associated with mitochondrial function. Moreover, T-2 toxin induced cell apoptosis by upregulating the expression of Cyt c, Bax, cleaved-caspase-9, and cleaved-caspase-3 proteins. In T-2 toxin-induced injury to the ovarian granulosa AVG-16 cells at concentrations of 10, 40 and 160 nM, not only were the previously mentioned effects observed, but also a decrease in mitochondrial membrane potential, ATP content, and an elevation in ROS levels. However, downregulating CUFF.253988.1 reversed T-2 toxin's inhibition of the SIRT3/PGC1-α pathway, alleviating mitochondrial dysfunction and reducing cell apoptosis. Notably, this may be attributed to the inhibition of T-2 toxin-induced enrichment of CUFF.253988.1 in mitochondria. In conclusion, CUFF.253988.1 plays a pivotal role in T-2 toxin-induced ovarian damage, operating through the inhibition of the SIRT3/PGC1-α pathway and promotion of cell apoptosis.
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Affiliation(s)
- Chenglin Yang
- Hunan Engineering Research Center of Livestock and Poultry Health Care, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China; Colleges of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China
| | - Hui Fan
- Hunan Engineering Research Center of Livestock and Poultry Health Care, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China; Colleges of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China
| | - You Wu
- Hunan Engineering Research Center of Livestock and Poultry Health Care, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China; Colleges of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China
| | - Zengenni Liang
- Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, PR China; Longping Branch Graduate School, Hunan University, Changsha 410125, PR China
| | - Yongkang Wang
- Hunan Engineering Research Center of Livestock and Poultry Health Care, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China; Colleges of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China
| | - Aoao Wu
- Hunan Engineering Research Center of Livestock and Poultry Health Care, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China; Colleges of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China
| | - Yuanyuan Li
- Hunan Engineering Research Center of Livestock and Poultry Health Care, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China; Colleges of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China
| | - Zhihang Yuan
- Hunan Engineering Research Center of Livestock and Poultry Health Care, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China; Colleges of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China
| | - Jine Yi
- Hunan Engineering Research Center of Livestock and Poultry Health Care, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China; Colleges of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China
| | - Deming Yin
- Colleges of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China.
| | - Jing Wu
- Hunan Engineering Research Center of Livestock and Poultry Health Care, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China; Colleges of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China; Institute of Yunnan Circular Agricultural Industry, Puer 665000, PR China.
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12
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Zhang B, Wu H, Zhang J, Cong C, Zhang L. The study of the mechanism of non-coding RNA regulation of programmed cell death in diabetic cardiomyopathy. Mol Cell Biochem 2024; 479:1673-1696. [PMID: 38189880 DOI: 10.1007/s11010-023-04909-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 11/25/2023] [Indexed: 01/09/2024]
Abstract
Diabetic cardiomyopathy (DCM) represents a distinct myocardial disorder elicited by diabetes mellitus, characterized by aberrations in myocardial function and structural integrity. This pathological condition predominantly manifests in individuals with diabetes who do not have concurrent coronary artery disease or hypertension. An escalating body of scientific evidence substantiates the pivotal role of programmed cell death (PCD)-encompassing apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis-in the pathogenic progression of DCM, thereby emerging as a prospective therapeutic target. Additionally, numerous non-coding RNAs (ncRNAs) have been empirically verified to modulate the biological processes underlying programmed cell death, consequently influencing the evolution of DCM. This review systematically encapsulates prevalent types of PCD manifest in DCM as well as nascent discoveries regarding the regulatory influence of ncRNAs on programmed cell death in the pathogenesis of DCM, with the aim of furnishing novel insights for the furtherance of research in PCD-associated disorders relevant to DCM.
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Affiliation(s)
- Bingrui Zhang
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine Cardiovascular Department Cardiovascular Disease Research, Jinan, 250014, Shandong, China
| | - Hua Wu
- Tai'an Special Care Hospital Clinical Laboratory Medical Laboratory Direction, Tai'an, 271000, Shandong, China
| | - Jingwen Zhang
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine Cardiovascular Department Cardiovascular Disease Research, Jinan, 250014, Shandong, China
| | - Cong Cong
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine Cardiovascular Department Cardiovascular Disease Research, Jinan, 250014, Shandong, China
| | - Lin Zhang
- Tai'an Hospital of Chinese Medicine Cardiovascular Department Cardiovascular Disease Research, No.216, Yingxuan Street, Tai'an, 271000, Shandong, China.
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13
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Yao X, Huang X, Chen J, Lin W, Tian J. Roles of non-coding RNA in diabetic cardiomyopathy. Cardiovasc Diabetol 2024; 23:227. [PMID: 38951895 PMCID: PMC11218407 DOI: 10.1186/s12933-024-02252-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 04/26/2024] [Indexed: 07/03/2024] Open
Abstract
In recent years, the incidence of diabetes has been increasing rapidly, posing a serious threat to human health. Diabetic cardiomyopathy (DCM) is characterized by cardiomyocyte hypertrophy, myocardial fibrosis, apoptosis, ventricular remodeling, and cardiac dysfunction in individuals with diabetes, ultimately leading to heart failure and mortality. However, the underlying mechanisms contributing to DCM remain incompletely understood. With advancements in molecular biology technology, accumulating evidence has shown that numerous non-coding RNAs (ncRNAs) crucial roles in the development and progression of DCM. This review aims to summarize recent studies on the involvement of three types of ncRNAs (micro RNA, long ncRNA and circular RNA) in the pathophysiology of DCM, with the goal of providing innovative strategies for the prevention and treatment of DCM.
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Affiliation(s)
- Xi Yao
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Xinyue Huang
- International School of Medicine, International Institutes of Medicine, The 4th Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, 322000, China
| | - Jianghua Chen
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Weiqiang Lin
- International School of Medicine, International Institutes of Medicine, The 4th Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, 322000, China.
| | - Jingyan Tian
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Clinical Trials Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
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14
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Imran M, Abida, Eltaib L, Siddique MI, Kamal M, Asdaq SMB, Singla N, Al-Hajeili M, Alhakami FA, AlQarni AF, Abdulkhaliq AA, Rabaan AA. Beyond the genome: MALAT1's role in advancing urologic cancer care. Pathol Res Pract 2024; 256:155226. [PMID: 38452585 DOI: 10.1016/j.prp.2024.155226] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 02/07/2024] [Accepted: 02/21/2024] [Indexed: 03/09/2024]
Abstract
Urologic cancers (UCs), which include bladder, kidney, and prostate tumors, account for almost a quarter of all malignancies. Long non-coding RNAs (lncRNAs) are tissue-specific RNAs that influence cell growth, death, and division. LncRNAs are dysregulated in UCs, and their abnormal expression may allow them to be used in cancer detection, outlook, and therapy. With the identification of several novel lncRNAs and significant exploration of their functions in various illnesses, particularly cancer, the study of lncRNAs has evolved into a new obsession. MALAT1 is a flexible tumor regulator implicated in an array of biological activities and disorders, resulting in an important research issue. MALAT1 appears as a hotspot, having been linked to the dysregulation of cell communication, and is intimately linked to cancer genesis, advancement, and response to treatment. MALAT1 additionally operates as a competitive endogenous RNA, binding to microRNAs and resuming downstream mRNA transcription and operation. This regulatory system influences cell growth, apoptosis, motility, penetration, and cell cycle pausing. MALAT1's evaluation and prognosis significance are highlighted, with a thorough review of its manifestation levels in several UC situations and its association with clinicopathological markers. The investigation highlights MALAT1's adaptability as a possible treatment target, providing fresh ways for therapy in UCs as we integrate existing information The article not only gathers current knowledge on MALAT1's activities but also lays the groundwork for revolutionary advances in the treatment of UCs.
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Affiliation(s)
- Mohd Imran
- Department of Pharmaceutical Chemistry, College of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia.
| | - Abida
- Department of Pharmaceutical Chemistry, College of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia
| | - Lina Eltaib
- Department of Pharmaceutics, College of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia
| | - Muhammad Irfan Siddique
- Department of Pharmaceutics, College of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia
| | - Mehnaz Kamal
- Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | | | - Neelam Singla
- School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Mahal Road, Jaipur 302017, India
| | - Marwan Al-Hajeili
- Department of Medicine, King Abdulaziz University, Jeddah 23624, Saudi Arabia
| | - Fatemah Abdulaziz Alhakami
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Saudi Arabia
| | - Ahmed Farhan AlQarni
- Histopathology Laboratory, Najran Armed Forces Hospital, Najran 66251, Saudi Arabia
| | - Altaf A Abdulkhaliq
- Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia
| | - Ali A Rabaan
- Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia; College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; Department of Public Health and Nutrition, The University of Haripur, Haripur 22610, Pakistan
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15
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Zhao M, Wang T, Cai X, Li G, Li N, Zhou H. LncRNA and mRNA expression characteristic and bioinformatic analysis in myocardium of diabetic cardiomyopathy mice. BMC Genomics 2024; 25:312. [PMID: 38532337 DOI: 10.1186/s12864-024-10235-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Accepted: 03/18/2024] [Indexed: 03/28/2024] Open
Abstract
BACKGROUND Diabetic cardiomyopathy (DCM) is becoming a very well-known clinical entity and leads to increased heart failure in diabetic patients. Long non-coding RNAs (LncRNAs) play an important role in the pathogenesis of DCM. In the present study, the expression profiles of lncRNAs and mRNAs were illuminated in myocardium from DCM mice, with purpose of exploring probable pathological processes of DCM involved by differentially expressed genes in order to provide a new direction for the future researches of DCM. RESULTS The results showed that a total of 93 differentially expressed lncRNA transcripts and 881 mRNA transcripts were aberrantly expressed in db/db mice compared with the controls. The top 6 differentially expressed lncRNAs like up-regulated Hmga1b, Gm8909, Gm50252 and down-regulated Msantd4, 4933413J09Rik, Gm41414 have not yet been reported in DCM. The lncRNAs-mRNAs co-expression network analysis showed that LncRNA 2610507I01Rik, 2310015A16Rik, Gm10503, A930015D03Rik and Gm48483 were the most relevant to differentially expressed mRNAs. CONCLUSION Our results showed that db/db DCM mice exist differentially expressed lncRNAs and mRNAs in hearts. These differentially expressed lncRNAs may be involved in the pathological process of cardiomyocyte apoptosis and fibrosis in DCM.
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Affiliation(s)
- Mengnan Zhao
- Department of Endocrinology, The Second Hospital of Hebei Medical University, No. 215, Hepingxi Road, Xinhua District, 050000, Shijiazhuang, Hebei, China
| | - Ting Wang
- Department of Endocrinology, The Second Hospital of Hebei Medical University, No. 215, Hepingxi Road, Xinhua District, 050000, Shijiazhuang, Hebei, China
| | - Xiaoning Cai
- Department of Endocrinology, Liaocheng Traditional Chinese Medicine Hospital, No. 1, Wenhua Road, Dongchangfu District, 252000, Liaocheng, Shandong, China
| | - Guizhi Li
- Department of Endocrinology, The Second Hospital of Hebei Medical University, No. 215, Hepingxi Road, Xinhua District, 050000, Shijiazhuang, Hebei, China
| | - Na Li
- Department of Endocrinology, The Second Hospital of Hebei Medical University, No. 215, Hepingxi Road, Xinhua District, 050000, Shijiazhuang, Hebei, China
| | - Hong Zhou
- Department of Endocrinology, The Second Hospital of Hebei Medical University, No. 215, Hepingxi Road, Xinhua District, 050000, Shijiazhuang, Hebei, China.
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Han LL, Wang SH, Yao MY, Zhou H. Urinary exosomal microRNA-145-5p and microRNA-27a-3p act as noninvasive diagnostic biomarkers for diabetic kidney disease. World J Diabetes 2024; 15:92-104. [PMID: 38313849 PMCID: PMC10835498 DOI: 10.4239/wjd.v15.i1.92] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 11/27/2023] [Accepted: 12/25/2023] [Indexed: 01/12/2024] Open
Abstract
BACKGROUND Diabetic kidney disease (DKD), characterized by increased urinary microalbumin levels and decreased renal function, is the primary cause of end-stage renal disease. Its pathological mechanisms are complicated and multifactorial; Therefore, sensitive and specific biomarkers are needed. Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney. The microRNAs (miRNAs) in urinary exosome are remarkably stable and highly tissue-specific for the kidney. AIM To determine if urinary exosomal miRNAs from diabetic patients can serve as noninvasive biomarkers for early DKD diagnosis. METHODS Type 2 diabetic mellitus (T2DM) patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups: DM, diabetic patients without albuminuria [urinary albumin to creatinine ratio (UACR) < 30 mg/g] and DKD, diabetic patients with albuminuria (UACR ≥ 30 mg/g). Healthy subjects were the normal control (NC) group. Urinary exosomal miR-145-5p, miR-27a-3p, and miR-29c-3p, were detected using real-time quantitative polymerase chain reaction. The correlation between exosomal miRNAs and the clinical indexes was evaluated. The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic (ROC) analysis. Biological functions of miR-145-5p were investigated by performing Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. RESULTS Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group (miR-145-5p: 4.54 ± 1.45 vs 1.95 ± 0.93, P < 0.001; miR-27a-3p: 2.33 ± 0.79 vs 1.71 ± 0.76, P < 0.05) and the NC group (miR-145-5p: 4.54 ± 1.45 vs 1.55 ± 0.83, P < 0.001; miR-27a-3p: 2.33 ± 0.79 vs 1.10 ± 0.51, P < 0.001). The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate. miR-27a-3p was also closely related to blood glucose, glycosylated hemoglobin A1c, and low-density lipoprotein cholesterol. ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88 [95% confidence interval (CI): 0.784-0.985, P < 0.0001] in diagnosing DKD than miR-27a-3p with 0.71 (95%CI: 0.547-0.871, P = 0.0239). Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament, cytoskeleton, and extracellular exosome and were involved in the pathological processes of DKD, including apoptosis, inflammation, and fibrosis. CONCLUSION Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.
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Affiliation(s)
- Lu-Lu Han
- Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
- Department of Endocrinology, Baoding No. 1 Central Hospital, Baoding 071000, Hebei Province, China
| | - Sheng-Hai Wang
- Department of Critical Care Medicine, The Affiliated Hospital of Hebei University, Baoding 071000, Hebei Province, China
| | - Ming-Yan Yao
- Department of Endocrinology, Baoding No. 1 Central Hospital, Baoding 071000, Hebei Province, China
| | - Hong Zhou
- Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
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