Volume 12, Issue 3 (Vol.12 No.3 Oct 2023)                   rbmb.net 2023, 12(3): 448-457 | Back to browse issues page

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Niknam N, Nikooei S, Ghasemi H, Zadian S S, Goudarzi K, Ahmadi S M et al . Circulating Levels of HOTAIR- lncRNA Are Associated with Disease Progression and Clinical Parameters in Type 2 Diabetes Patients. rbmb.net 2023; 12 (3) :448-457
URL: http://rbmb.net/article-1-1262-en.html
Department of Laboratory Sciences, Faculty of Paramedicine, Yasuj University of Medical Sciences, Yasuj, Iran.
Abstract:   (615 Views)
Background: Recent studies have implicated dysregulated long non-coding RNA (lncRNA) levels in the pathogenesis of type 2 diabetes (T2D). This study aimed to assess the expression of circulating HOTAIR and uc.48+, examining their correlation with clinical and biochemical variables in T2D patients, pre-diabetic individuals, and healthy controls.

Methods: Peripheral blood levels of lncRNAs were quantified using QRT-PCR in 65 T2D patients, 63 pre-diabetic individuals, and 63 healthy subjects. Pathway enrichment analysis was conducted to explore the functional enrichment of lncRNA-miRNA targets.

Results: Analysis revealed a significantly elevated circulating level of HOTAIR in both T2D (P < 0.0001) and pre-diabetic patients (P = 0.04) compared to controls. ROC analysis demonstrated that, at a cutoff value of 9.1, with a sensitivity of 80% and specificity of 62%, HOTAIR could distinguish T2D patients from controls (AUC = 0.723, 95% CI 0.637-0.799, P < 0.0001). Spearman correlation analysis identified a significant positive correlation between HOTAIR expression, HbA1c, and insulin resistance (P < 0.005). MiRNA enrichment analysis indicated significant enrichment of diabetes-related pathways among HOTAIR's miRNA targets. Conversely, no significant difference in uc.48+ circulating levels between groups was observed, but a significant positive correlation emerged between uc.48+ and systolic blood pressure.

Conclusions: This study provides evidence that elevated HOTAIR expression levels are associated with T2D progression, suggesting their potential as biomarkers for early diagnosis and prognosis.

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Type of Article: Original Article | Subject: Biochemistry
Received: 2023/09/30 | Accepted: 2023/12/27 | Published: 2024/02/25

References
1. Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. IDF Diabetes Atlas Committee. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843. [DOI:10.1016/j.diabres.2019.107843] [PMID]
2. Rezaeinejad F, Mirzaei A, Khalvati B, Sabz G, Alipoor B. Circulating expression levels of CircHIPK3 and CDR1as circular-RNAs in type 2 diabetes patients. Mol Biol Rep. 2022;49(1):131-138. [DOI:10.1007/s11033-021-06850-8] [PMID]
3. Alipoor B, Nikouei S, Rezaeinejad F, Malakooti-Dehkordi SN, Sabati Z, Ghasemi H. Long non-coding RNAs in metabolic disorders: pathogenetic relevance and potential biomarkers and therapeutic targets. J Endocrinol Invest. 2021;44(10):2015-2041. [DOI:10.1007/s40618-021-01559-8] [PMID]
4. Medhat E, Ayeldeen G, Hosni Ahmed H, Shaker O, Gheita T, Salama Ashour S. HOTAIR and THRIL Long Non Coding RNAs and Their Target Genes in Rheumatoid Arthritis patients. Rep Biochem Mol Biol. 2022;10(4):614-621. [DOI:10.52547/rbmb.10.4.697] [PMID] []
5. Rajabi A, Dastmalchi N, Shokri N, Tayefeh-Gholami S, Yaghoubi SM, Safaralizadeh R. Expression Level of lncRNA CYTOR in Iranian Cervical Cancer Patients. Rep Biochem Mol Biol. 2023;12(1):120-126.
6. Yang Y, Lv X, Fan Q, Wang X, Xu L, Lu X, Chen T. Analysis of circulating lncRNA expression profiles in patients with diabetes mellitus and diabetic nephropathy: Differential expression profile of circulating lncRNA
. Clin Nephrol. 2019;92(1):25-35. [DOI:10.5414/CN109525] [PMID]
7. Parvar SN, Mirzaei A, Zare A, Doustimotlagh AH, Nikooei S, Arya A, Alipoor B. Effect of metformin on the long non-coding RNA expression levels in type 2 diabetes: an in vitro and clinical trial study. Pharmacol Rep. 2023;75(1):189-198. [DOI:10.1007/s43440-022-00427-3] [PMID]
8. Ding L, Gong C, Zhao J, Liu X, Li T, Rao S, Wang S, Liu Y, Peng S, Xiao W, Xiong C, Wang R, Liang S, Xu H. Noncoding transcribed ultraconserved region (T-UCR) UC.48+ is a novel regulator of high-fat diet induced myocardial ischemia/reperfusion injury. J Cell Physiol. 2019;234(6):9849-9861. [DOI:10.1002/jcp.27674] [PMID]
9. Li Z, Li X, Chen X, Li S, Ho IHT, Liu X, Chan MTV, Wu WKK. Emerging roles of long non-coding RNAs in neuropathic pain. Cell Prolif. 2019;52(1):e12528. [DOI:10.1111/cpr.12528] [PMID] []
10. Teng X, Chen X, Xue H, Tang Y, Zhang P, Kang Q, et al. NPInter v4.0: an integrated database of ncRNA interactions. Nucleic Acids Res. 2020 Jan 8;48(D1):D160-D165. [DOI:10.1093/nar/gkz969] [PMID] []
11. Huang HY, Lin YC, Li J, Huang KY, Shrestha S, Hong HC, et al. miRTarBase 2020: updates to the experimentally validated microRNA-target interaction database. Nucleic Acids Res. 2020;48(D1):D148-D154. [DOI:10.1093/nar/gkz896] [PMID] []
12. Sherman BT, Hao M, Qiu J, Jiao X, Baseler MW, Lane HC, et al. DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res. 2022;50(W1):W216-W221. [DOI:10.1093/nar/gkac194] [PMID] []
13. Kern F, Fehlmann T, Solomon J, Schwed L, Grammes N, Backes C, et al. miEAA 2.0: integrating multi-species microRNA enrichment analysis and workflow management systems. Nucleic Acids Res. 2020;48(W1):W521-W8. [DOI:10.1093/nar/gkaa309] [PMID] []
14. Sathishkumar C, Prabu P, Mohan V, Balasubramanyam M. Linking a role of lncRNAs (long non-coding RNAs) with insulin resistance, accelerated senescence, and inflammation in patients with type 2 diabetes. Hum genomics. 2018;12(1):1-9. [DOI:10.1186/s40246-018-0173-3] [PMID] []
15. Wang H, Xia Y, Zhang Y. Diagnostic significance of serum lncRNA HOTAIR and its predictive value for the development of chronic complications in patients with type 2 diabetes mellitus. Diabetol Metab Syndr. 2021;13(1):1-6. [DOI:10.1186/s13098-021-00719-3] [PMID] []
16. Li M, Guo Y, Wang X, Duan B, Li L. HOTAIR participates in hepatic insulin resistance via regulating SIRT1. Eur Rev Med Pharmacol Sci. 2018;22(22).
17. argazi S, Ravanbakhsh M, Nia MH, Mirinejad S, Sheervalilou R, Majidpour M, Danesh H, Saravani R. Association of Polymorphisms within HOX Transcript Antisense RNA (HOTAIR) with Type 2 Diabetes Mellitus and Laboratory Characteristics: A Preliminary Case-Control Study. Dis Markers. 2022;2022:4327342. [DOI:10.1155/2022/4327342] [PMID] []
18. Misra A, Gopalan H, Jayawardena R, Hills AP, Soares M, Reza-Albarrán AA, Ramaiya KL. Diabetes in developing countries. J Diabetes. 2019;11(7):522-539. [DOI:10.1111/1753-0407.12913] [PMID]
19. Abdulle LE, Hao J-l, Pant OP, Liu X-f, Zhou D-d, Gao Y, et al. MALAT1 as a diagnostic and therapeutic target in diabetes-related complications: a promising long-noncoding RNA. Int J Med Sci. 2019;16(4):548. [DOI:10.7150/ijms.30097] [PMID] []
20. Biswas S, Feng B, Chen S, Liu J, Aref-Eshghi E, Gonder J, Ngo V, Sadikovic B, Chakrabarti S. The Long Non-Coding RNA HOTAIR Is a Critical Epigenetic Mediator of Angiogenesis in Diabetic Retinopathy. Invest Ophthalmol Vis Sci. 2021;62(3):20. [DOI:10.1167/iovs.62.3.20] [PMID] []
21. Qi K, Zhong J. LncRNA HOTAIR improves diabetic cardiomyopathy by increasing viability of cardiomyocytes through activation of the PI3K/Akt pathway. Exp Ther Med. 2018;16(6):4817-23. [DOI:10.3892/etm.2018.6755] [PMID] []
22. Xiong J, Zhou Q. The lncRNA HOTAIR attenuates pyroptosis of diabetic cardiomyocytes by recruiting FUS to regulate SIRT3 expression. Kaohsiung J Med Sci. 2023;39(5):458-467. [DOI:10.1002/kjm2.12676] [PMID]
23. Chen Y, Huang C, Zhu SY, Zou HC, Xu CY, Chen YX. Overexpression of HOTAIR attenuates Pi-induced vascular calcification by inhibiting Wnt/β-catenin through regulating miR-126/Klotho/SIRT1 axis. Mol Cell Biochem. 2021;476(10):3551-3561. [DOI:10.1007/s11010-021-04164-8] [PMID]
24. Shaker OG, Abdelaleem OO, Mahmoud RH, Abdelghaffar NK, Ahmed TI, Said OM, Zaki OM. Diagnostic and prognostic role of serum miR-20b, miR-17-3p, HOTAIR, and MALAT1 in diabetic retinopathy. IUBMB Life. 2019;71(3):310-320. [DOI:10.1002/iub.1970] [PMID]
25. Su R, Wu X, Ke F. Long Non-Coding RNA HOTAIR Expression and Clinical Significance in Patients with Gestational Diabetes. Int J Gen Med. 2021;14:9945-9950. [DOI:10.2147/IJGM.S341106] [PMID] []
26. Wu X, Su R. Long non-coding RNA myocardial infarction associated transcript expression and clinical significance in patients with hypertension during pregnancy. Ir J Med Sci. 2022;191(5):2223-2228. [DOI:10.1007/s11845-021-02811-z] [PMID]
27. Obaid M, Udden SMN, Alluri P, Mandal SS. LncRNA HOTAIR regulates glucose transporter Glut1 expression and glucose uptake in macrophages during inflammation. Sci Rep. 2021;11(1):232. [DOI:10.1038/s41598-020-80291-4] [PMID] []
28. Zhu HP. Silence of HOTAIR inhibits insulin secretion and proliferation in pancreatic β cells. Eur Rev Med Pharmacol Sci. 2020;24(2):784-792.
29. Li D, Zhang J, Li J. Role of miRNA sponges in hepatocellular carcinoma. Clin Chim Acta. 2020;500:10-19. [DOI:10.1016/j.cca.2019.09.013] [PMID]
30. Khokhar M, Roy D, Modi A, Agarwal R, Yadav D, Purohit P, et al. Perspectives on the role of PTEN in diabetic nephropathy: an update. Crit Rev Clin Lab Sci. 2020;57(7):470-83. [DOI:10.1080/10408363.2020.1746735] [PMID]
31. Ren H, Shao Y, Wu C, Ma X, Lv C, Wang Q. Metformin alleviates oxidative stress and enhances autophagy in diabetic kidney disease via AMPK/SIRT1-FoxO1 pathway. Mol Cell Endocrinol. 2020;500:110628. [DOI:10.1016/j.mce.2019.110628] [PMID]
32. Honzawa N, Fujimoto K. The Plasticity of Pancreatic β-Cells. Metabolites. 2021;11(4):218. [DOI:10.3390/metabo11040218] [PMID] []
33. Xiong W, Huang L, Shen Y, Guan S, He L, Tong Z, et al. Effects of lncRNA uc.48+ siRNA on the release of CGRP in the spinal cords of rats with diabetic neuropathic pain. Int J Clin Exp Pathol. 2017;10(9):9960-9969.
34. Wu H, Jiang M, Liu Q, Wen F, Nie Y. lncRNA uc.48+ regulates immune and inflammatory reactions mediated by the P2X(7) receptor in type 2 diabetic mice. Exp Ther Med. 2020;20(6):230. [DOI:10.3892/etm.2020.9360] [PMID] []

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