Online first
Review article
Published online: 2024-07-04

open access

Page views 67
Article views/downloads 38
Get Citation

Connect on Social Media

Connect on Social Media

Therapeutic Landscape of Diabetic Nephropathy: Insights from Long Noncoding RNAs

Md Sadique Hussain1, Mudasir Maqbool2, Nusrat K. Shaikh3, Mohit Agrawal4, Ayesha Sultana5


Objective: Diabetic nephropathy (DN) is a major complication of diabetes mellitus and a leading cause of endstage renal disease. Long noncoding RNAs (lncRNAs) have emerged as critical regulators in various biological processes, including those implicated in DN pathogenesis. This manuscript provides a comprehensive review of the therapeutic potential of lncRNAs in the context of DN, elucidating their roles as diagnostic markers, prognostic indicators, and therapeutic targets. Materials and methods: A systematic review of current literature was conducted, focusing on studies investigating the involvement of lncRNAs in DN pathophysiology and therapeutic interventions. The literature search was performed in Medline, Scopus, WOS, and PubMed databases. Key findings related to the regulatory mechanisms of lncRNAs in DN progression and their modulation by pharmacological agents or gene therapy approaches were synthesized. Results: This extensive analysis examines the many functions of lncRNAs in DN, including their participation in crucial physiological mechanisms. The analysis systematically examines the abnormal functioning of certain lncRNAs in the progression of DN, with a focus on their possible use as indicators for diagnosis and prognosis. Furthermore, we examine the molecular mechanisms by which lncRNAs regulate the course of DN. Conclusions: Understanding the intricate roles of lncRNAs in DN pathogenesis opens avenues for the development of novel diagnostic tools and therapeutic interventions. Targeting dysregulated lncRNAs holds considerable promise in mitigating DN progression and improving clinical outcomes for patients with diabetic kidney disease. Further research efforts are warranted to validate the clinical utility of lncRNA-based therapeutics in DN management.

Article available in PDF format

View PDF Download PDF file


  1. Reidy K, Kang HMi, Hostetter T, et al. Molecular mechanisms of diabetic kidney disease. J Clin Invest. 2014; 124(6): 2333–2340.
  2. Lassén E, Daehn IS. Molecular Mechanisms in Early Diabetic Kidney Disease: Glomerular Endothelial Cell Dysfunction. Int J Mol Sci. 2020; 21(24).
  3. Hussain MdS, Gupta G, Goyal A, et al. From nature to therapy: Luteolin's potential as an immune system modulator in inflammatory disorders. J Biochem Mol Toxicol. 2023; 37(11): e23482.
  4. Bahl G, Hussain M, Saraswat N, et al. Beyond Diabetes Management: Unraveling Metformin’s Long-Term Effects on Vitamin B12. Clin Diabetol. 2023; 12(5): 279–282.
  5. Yang D, Livingston MJ, Liu Z, et al. Autophagy in diabetic kidney disease: regulation, pathological role and therapeutic potential. Cell Mol Life Sci. 2018; 75(4): 669–688.
  6. Cao Z, Cooper ME. Pathogenesis of diabetic nephropathy. J Diabetes Investig. 2011; 2(4): 243–247.
  7. Demarest KT, Riegle GD, Moore KE. Prolactin-induced activation of tuberoinfundibular dopaminergic neurons: evidence for both a rapid 'tonic' and a delayed 'induction' component. Neuroendocrinology. 1984; 38(6): 467–475.
  8. Hussain MdS, Altamimi AS, Afzal M, et al. Kaempferol: Paving the path for advanced treatments in aging-related diseases. Exp Gerontol. 2024; 188: 112389.
  9. Fu H, Liu S, Bastacky SI, et al. Diabetic kidney diseases revisited: A new perspective for a new era. Mol Metab. 2019; 30: 250–263.
  10. Hussain MdS, Sharma G. The Burden of Cardiovascular Diseases Due to COVID-19 Pandemic. Thorac Cardiovasc Surg. 2024; 72(1): 40–50.
  11. Bahl G, Upadhyay D, Varma M, et al. Chronic Calcific Pancreatitis Presented with Secondary Diabetes and Diabetic Ketoacidosis: A Case Report. Clin Diabetol. 2023; 12(3): 209–211.
  12. Wang W, Sun W, Cheng Y, et al. Role of sirtuin-1 in diabetic nephropathy. J Mol Med (Berl). 2019; 97(3): 291–309.
  13. Parmar UM, Jalgaonkar MP, Kulkarni YA, et al. Autophagy-nutrient sensing pathways in diabetic complications. Pharmacol Res. 2022; 184: 106408.
  14. Kumar M, Hussain M, Raj S, et al. An Overview of Treatment Modalities and Management Aspects for Obesity. Current Nutrition & Food Science. 2023; 19(2): 105–113.
  15. Bahl G, Hussain M, Upadhyay D, et al. Chronic Calcific Pancreatitis and Its Association With Secondary Diabetes Mellitus. J Endocrinol Metab. 2023; 13(3): 89–95.
  16. Lv J, Wu Yu, Mai Y, et al. Noncoding RNAs in Diabetic Nephropathy: Pathogenesis, Biomarkers, and Therapy. J Diabetes Res. 2020; 2020: 3960857.
  17. Hussain MdS, Afzal O, Gupta G, et al. Probing the links: Long non-coding RNAs and NF-κB signalling in atherosclerosis. Pathol Res Pract. 2023; 249: 154773.
  18. Loganathan T, Sulaiman S, Murad N, et al. Urinary Long Noncoding RNAs (lncRNAs) as Biomarkers for Diabetic Nephropathy in Malaysian Type 2 Diabetes Patients. American Heart Journal. 2020; 229: 169–170.
  19. Alvarez ML, Distefano JK. The role of non-coding RNAs in diabetic nephropathy: potential applications as biomarkers for disease development and progression. Diabetes Res Clin Pract. 2013; 99(1): 1–11.
  20. Chen L, Wu B, Wang S, et al. Identification of Cooperative Gene Regulation Among Transcription Factors, LncRNAs, and MicroRNAs in Diabetic Nephropathy Progression. Front Genet. 2020; 11: 1008.
  21. Durge A, Sharma I, Tupe RS. Glycation-Associated Diabetic Nephropathy and the Role of Long Noncoding RNAs. Biomedicines. 2022; 10(10).
  22. Guo M, Dai Y, Jiang L, et al. Bioinformatics Analysis of the Mechanisms of Diabetic Nephropathy Novel Biomarkers and Competing Endogenous RNA Network. Front Endocrinol (Lausanne). 2022; 13: 934022.
  23. Bonasio R, Shiekhattar R. Regulation of transcription by long noncoding RNAs. Annu Rev Genet. 2014; 48: 433–455.
  24. Chen A, Yu R, Jiang S, et al. Recent Advances of MicroRNAs, Long Non-coding RNAs, and Circular RNAs in Preeclampsia. Front Physiol. 2021; 12: 659638.
  25. Hussain MdS, Gupta G, Afzal M, et al. Exploring the role of lncrna neat1 knockdown in regulating apoptosis across multiple cancer types: A review. Pathol Res Pract. 2023; 252: 154908.
  26. Yang J, Yang FJ, Wang YG, et al. LncRNA MIR497HG inhibits proliferation and migration of retinal endothelial cells under high-level glucose treatment via miRNA-128-3p/SIRT1 axis. Eur Rev Med Pharmacol Sci. 2020; 24(11): 5871–5877.
  27. Hussain MdS, Shaikh NK, Agrawal M, et al. Osteomyelitis and non-coding RNAS: A new dimension in disease understanding. Pathol Res Pract. 2024; 255: 155186.
  28. Selleri L, Bartolomei MS, Bickmore WA, et al. A Hox-Embedded Long Noncoding RNA: Is It All Hot Air? PLoS Genet. 2016; 12(12): e1006485.
  29. Han X, Luo S, Peng G, et al. Mouse knockout models reveal largely dispensable but context-dependent functions of lncRNAs during development. J Mol Cell Biol. 2018; 10(2): 175–178.
  30. Sauvageau M, Goff LA, Lodato S, et al. Multiple knockout mouse models reveal lincRNAs are required for life and brain development. Elife. 2013; 2: e01749.
  31. Hussain MdS, Moglad E, Afzal M, et al. Circular RNAs in the KRAS pathway: Emerging players in cancer progression. Pathol Res Pract. 2024; 256: 155259.
  32. Xiang JF, Yin QF, Chen T, et al. Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions at the MYC locus. Cell Res. 2014; 24(5): 513–531.
  33. Postepska-Igielska A, Giwojna A, Gasri-Plotnitsky L, et al. LncRNA Khps1 Regulates Expression of the Proto-oncogene SPHK1 via Triplex-Mediated Changes in Chromatin Structure. Mol Cell. 2015; 60(4): 626–636.
  34. Wang KC, Yang YW, Liu Bo, et al. A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature. 2011; 472(7341): 120–124.
  35. Sati S, Ghosh S, Jain V, et al. Genome-wide analysis reveals distinct patterns of epigenetic features in long non-coding RNA loci. Nucleic Acids Res. 2012; 40(20): 10018–10031.
  36. Grote P, Wittler L, Hendrix D, et al. The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse. Dev Cell. 2013; 24(2): 206–214.
  37. Gonzalez I, Munita R, Agirre E, et al. A lncRNA regulates alternative splicing via establishment of a splicing-specific chromatin signature. Nat Struct Mol Biol. 2015; 22(5): 370–376.
  38. Froberg JE, Yang L, Lee JT. Guided by RNAs: X-inactivation as a model for lncRNA function. J Mol Biol. 2013; 425(19): 3698–3706.
  39. Samata M, Akhtar A. Dosage Compensation of the X Chromosome: A Complex Epigenetic Assignment Involving Chromatin Regulators and Long Noncoding RNAs. Annu Rev Biochem. 2018; 87: 323–350.
  40. Engreitz JM, Haines JE, Perez EM, et al. Local regulation of gene expression by lncRNA promoters, transcription and splicing. Nature. 2016; 539(7629): 452–455.
  41. Kim TK, Hemberg M, Gray JM, et al. Widespread transcription at neuronal activity-regulated enhancers. Nature. 2010; 465(7295): 182–187.
  42. Li W, Notani D, Rosenfeld MG. Enhancers as non-coding RNA transcription units: recent insights and future perspectives. Nat Rev Genet. 2016; 17(4): 207–223.
  43. Hussain MdS, Afzal O, Gupta G, et al. Long non-coding RNAs in lung cancer: Unraveling the molecular modulators of MAPK signaling. Pathol Res Pract. 2023; 249: 154738.
  44. Jalali S, Jayaraj GG, Scaria V. Integrative transcriptome analysis suggest processing of a subset of long non-coding RNAs to small RNAs. Biol Direct. 2012; 7: 25.
  45. Song Hu, Xu Y, Shi L, et al. LncRNA THOR increases the stemness of gastric cancer cells via enhancing SOX9 mRNA stability. Biomed Pharmacother. 2018; 108: 338–346.
  46. Yang F, Xue X, Zheng L, et al. Long non-coding RNA GHET1 promotes gastric carcinoma cell proliferation by increasing c-Myc mRNA stability. FEBS J. 2014; 281(3): 802–813.
  47. Sen R, Ghosal S, Das S, et al. Competing endogenous RNA: the key to posttranscriptional regulation. ScientificWorldJournal. 2014; 2014: 896206.
  48. Liang WC, Fu WM, Wong CW, et al. The lncRNA H19 promotes epithelial to mesenchymal transition by functioning as miRNA sponges in colorectal cancer. Oncotarget. 2015; 6(26): 22513–22525.
  49. Han TS, Hur K, Cho HS, et al. Epigenetic Associations between lncRNA/circRNA and miRNA in Hepatocellular Carcinoma. Cancers (Basel). 2020; 12(9).
  50. Thomson DW, Dinger ME. Endogenous microRNA sponges: evidence and controversy. Nat Rev Genet. 2016; 17(5): 272–283.
  51. Jarlstad Olesen MT, S Kristensen L. Circular RNAs as microRNA sponges: evidence and controversies. Essays Biochem. 2021; 65(4): 685–696.
  52. Hussain MdS, Altamimi ASA, Afzal M, et al. From carcinogenesis to therapeutic avenues: lncRNAs and mTOR crosstalk in lung cancer. Pathol Res Pract. 2024; 253: 155015.
  53. Kim TK, Hemberg M, Gray JM. Enhancer RNAs: a class of long noncoding RNAs synthesized at enhancers. Cold Spring Harb Perspect Biol. 2015; 7(1): a018622.
  54. Geisler S, Coller J. RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts. Nat Rev Mol Cell Biol. 2013; 14(11): 699–712.
  55. Tsai MC, Manor O, Wan Y, et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science. 2010; 329(5992): 689–693.
  56. Neumann P, Jaé N, Knau A, et al. The lncRNA GATA6-AS epigenetically regulates endothelial gene expression via interaction with LOXL2. Nat Commun. 2018; 9(1): 237.
  57. Pandey A, Ajgaonkar S, Jadhav N, et al. Current Insights into miRNA and lncRNA Dysregulation in Diabetes: Signal Transduction, Clinical Trials and Biomarker Discovery. Pharmaceuticals (Basel). 2022; 15(10).
  58. Feng Y, Chen S, Xu J, et al. Dysregulation of lncRNAs GM5524 and GM15645 involved in high‑glucose‑induced podocyte apoptosis and autophagy in diabetic nephropathy. Mol Med Rep. 2018; 18(4): 3657–3664.
  59. Liu Y, Zhang M, Zhong H, et al. LncRNA SNHG16 regulates RAS and NF-κB pathway-mediated NLRP3 inflammasome activation to aggravate diabetes nephropathy through stabilizing TLR4. Acta Diabetol. 2023; 60(4): 563–577.
  60. Dieter C, Lemos NE, Girardi E, et al. The lncRNA MALAT1 is upregulated in urine of type 1 diabetes mellitus patients with diabetic kidney disease. Genet Mol Biol. 2023; 46(2): e20220291.
  61. Sun He, Chen T, Li X, et al. The relevance of the non-invasive biomarkers lncRNA GAS5/miR-21 ceRNA regulatory network in the early identification of diabetes and diabetic nephropathy. Diabetol Metab Syndr. 2023; 15(1): 197.
  62. Imamura K, Imamachi N, Akizuki G, et al. Long noncoding RNA NEAT1-dependent SFPQ relocation from promoter region to paraspeckle mediates IL8 expression upon immune stimul. Moll Cell. 2014; 53(3): 393–406.
  63. Hussain MdS, Afzal O, Gupta G, et al. Unraveling NEAT1's complex role in lung cancer biology: a comprehensive review. EXCLI J. 2024; 23: 34–52.
  64. Hussain MdS, Sharma P, Dhanjal DS, et al. Nanotechnology based advanced therapeutic strategies for targeting interleukins in chronic respiratory diseases. Chem Biol Interact. 2021; 348: 109637.
  65. Yu T-M, Palanisamy K, Sun K-T, et al. RANTES mediates kidney ischemia reperfusion injury through a possible role of HIF-1α and LncRNA PRINS. Sci Rep. 2016; 4(6): 18424.
  66. Wang P, Luo M-L, Song E, et al. Long noncoding RNA lnc-TSI inhibits renal fibrogenesis by negatively regulating the TGF-β/Smad3 pathway. Sci Transl Med. 2018; 10(462): eaat2039.
  67. Wu Y, Liu J, Zheng Y, et al. Suppressed expression of long non-coding RNA HOTAIR inhibits proliferation and tumourigenicity of renal carcinoma cells. Tumour Biol. 2014; 35(12): 11887–11894.
  68. Xiao ZD, Han L, Lee H, et al. LncRNA NBR2 engages a metabolic checkpoint by regulating AMPK under energy stress. Nat Cell Biol. 2017; 8(1): 783.
  69. Wu Y, Wang YQ, Weng WW, et al. A serum-circulating long noncoding RNA signature can discriminate between patients with clear cell renal cell carcinoma and healthy controls. Oncogenesis. 2016; 5(2): e192.
  70. Alicic R, Rooney M, Tuttle K. Diabetic Kidney Disease. Challenges, progress, and possibilities. Clinical Journal of the American Society of Nephrology. 2017; 12(12): 2032–2045.
  71. Ritz E, Orth S. Nephropathy in Patients with Type 2 Diabetes Mellitus. N Engl J Med. 1999; 341(15): 1127–1133.
  72. Long J, Badal SS, Ye Z, et al. Long noncoding RNA Tug1 regulates mitochondrial bioenergetics in diabetic nephropathy. J Clin Invest. 2016; 126(11): 4205–4218.
  73. Reichelt-Wurm S, Pregler M, Wirtz T, et al. Glomerular expression pattern of long non-coding RNAs in the type 2 diabetes mellitus BTBR mouse model. Sci Rep. 2019; 9(1): 9765.
  74. Shang J, Wang S, Jiang Y, et al. Identification of key lncRNAs contributing to diabetic nephropathy by gene co-expression network analysis. Sci Rep. 2019; 9(1): 3328.
  75. Wen Li, Zhang Z, Peng R, et al. Whole transcriptome analysis of diabetic nephropathy in the db/db mouse model of type 2 diabetes. J Cell Biochem. 2019; 120(10): 17520–17533.
  76. Li S, Susztak K. The long noncoding RNA Tug1 connects metabolic changes with kidney disease in podocytes. J Clin Invest. 2016; 126(11): 4072–4075.
  77. Sun SiF, Tang PMK, Feng M, et al. Novel lncRNA Erbb4-IR promotes diabetic kidney injury in db/db mice by targeting miR-29b. Diabetes. 2018; 67(4): 731–744.
  78. Wang Bo, Komers R, Carew R, et al. Suppression of microRNA-29 expression by TGF-β1 promotes collagen expression and renal fibrosis. J Am Soc Nephrol. 2012; 23(2): 252–265.
  79. Long J, Danesh FR. Values and Limitations of Targeting lncRNAs in Diabetic Nephropathy. Diabetes. 2018; 67(4): 552–553.
  80. Li J, Jiang X, Duan L, et al. Long non-coding RNA MEG3 impacts diabetic nephropathy progression through sponging miR-145. Am J Transl Res. 2019; 11(10): 6691–6698.
  81. Al-Rugeebah A, Alanazi M, Parine NR. MEG3: an Oncogenic Long Non-coding RNA in Different Cancers. Pathol Oncol Res. 2019; 25(3): 859–874.
  82. Hussain MdS, Majami AA, Ali H, et al. The complex role of MEG3: An emerging long non-coding RNA in breast cancer. Pathol Res Pract. 2023; 251: 154850.
  83. Sathishkumar C, Prabu P, Mohan V, et al. 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): 41.
  84. Zha F, Qu X, Tang Bo, et al. Long non-coding RNA MEG3 promotes fibrosis and inflammatory response in diabetic nephropathy via miR-181a/Egr-1/TLR4 axis. Aging (Albany NY). 2019; 11(11): 3716–3730.
  85. Ge X, Xu B, Xu W, et al. Long noncoding RNA GAS5 inhibits cell proliferation and fibrosis in diabetic nephropathy by sponging miR-221 and modulating SIRT1 expression. Aging (Albany NY). 2019; 11(20): 8745–8759.
  86. Bible E. Sirt1 attenuates diabetic albuminuria. Nat Rev Nephrol. 2013; 9(12): 696.
  87. Zhang L, Zhao S, Zhu Y. Long noncoding RNA growth arrest-specific transcript 5 alleviates renal fibrosis in diabetic nephropathy by downregulating matrix metalloproteinase 9 through recruitment of enhancer of zeste homolog 2. FASEB J. 2020; 34(2): 2703–2714.
  88. Yang J, Shen Y, Yang X, et al. Silencing of long noncoding RNA XIST protects against renal interstitial fibrosis in diabetic nephropathy via microRNA-93-5p-mediated inhibition of CDKN1A. Am J Physiol Renal Physiol. 2019; 317(5): F1350–F1358.
  89. Long J, Wang Y, Wang W, et al. Identification of microRNA-93 as a novel regulator of vascular endothelial growth factor in hyperglycemic conditions. J Biol Chem. 2010; 285(30): 23457–23465.
  90. Badal SS, Wang Y, Long J, et al. MicroRNA-22 is a master regulator of bone morphogenetic protein-7/6 homeostasis in the kidney. Nat Commun. 2016; 7: 12076.
  91. Kato M, Wang M, Chen Z, et al. An endoplasmic reticulum stress-regulated lncRNA hosting a microRNA megacluster induces early features of diabetic nephropathy. Nat Commun. 2016; 7: 12864.
  92. Guo K, Lu J, Huang Y, et al. Protective role of PGC-1α in diabetic nephropathy is associated with the inhibition of ROS through mitochondrial dynamic remodeling. PLoS One. 2015; 10(4): e0125176.
  93. Kang HMi, Ahn SHo, Choi P, et al. Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development. Nat Med. 2015; 21(1): 37–46.
  94. Sharma K, Karl B, Mathew AV, et al. Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease. J Am Soc Nephrol. 2013; 24(11): 1901–1912.
  95. Young TL, Matsuda T, Cepko CL. The Noncoding RNA Taurine Upregulated Gene 1 Is Required for Differentiation of the Murine Retina. Curr Biol. 2005; 15(6): 501–512.
  96. Shen H, Ming Y, Xu C, et al. Deregulation of long noncoding RNA (TUG1) contributes to excessive podocytes apoptosis by activating endoplasmic reticulum stress in the development of diabetic nephropathy. J Cell Physiol. 2019; 234(9): 15123–15133.
  97. Fisher L. Retraction: Long non-coding RNA TUG1 alleviates high glucose induced podocyte inflammation, fibrosis and apoptosis in diabetic nephropathy via targeting the miR-27a-3p/E2F3 axis. RSC Advances. 2021; 11(9): 5244.
  98. Hu M, Wang R, Li X, et al. LncRNA MALAT1 is dysregulated in diabetic nephropathy and involved in high glucose-induced podocyte injury via its interplay with β-catenin. J Cell Mol Med. 2017; 21(11): 2732–2747.
  99. Li X, Zeng Li, Cao C, et al. Long noncoding RNA MALAT1 regulates renal tubular epithelial pyroptosis by modulated miR-23c targeting of ELAVL1 in diabetic nephropathy. Exp Cell Res. 2017; 350(2): 327–335.
  100. Gödel M, Hartleben B, Herbach N, et al. Role of mTOR in podocyte function and diabetic nephropathy in humans and mice. J Clin Invest. 2011; 121(6): 2197–2209.
  101. Huang S, Xu Y, Ge X, et al. Long noncoding RNA NEAT1 accelerates the proliferation and fibrosis in diabetic nephropathy through activating Akt/mTOR signaling pathway. J Cell Physiol. 2019; 234(7): 11200–11207.
  102. Lei J, Zhao L, Zhang Y, et al. High Glucose-Induced Podocyte Injury Involves Activation of Mammalian Target of Rapamycin (mTOR)-Induced Endoplasmic Reticulum (ER) Stress. Cell Physiol Biochem. 2018; 45(6): 2431–2443.
  103. Wang X, Xu Y, Zhu YC, et al. LncRNA NEAT1 promotes extracellular matrix accumulation and epithelial-to-mesenchymal transition by targeting miR-27b-3p and ZEB1 in diabetic nephropathy. J Cell Physiol. 2019; 234(8): 12926–12933.
  104. Schena FP, Serino G, Sallustio F. MicroRNAs in kidney diseases: new promising biomarkers for diagnosis and monitoring. Nephrol Dial Transplant. 2014; 29(4): 755–763.
  105. Hussain MdS, Moglad E, Bansal P, et al. Exploring the oncogenic and tumor-suppressive roles of Circ-ADAM9 in cancer. Pathol Res Pract. 2024; 256: 155257.
  106. Putta S, Lanting L, Sun G, et al. Inhibiting microRNA-192 ameliorates renal fibrosis in diabetic nephropathy. J Am Soc Nephrol. 2012; 23(3): 458–469.
  107. Gomez I, Nakagawa N, Duffield J. MicroRNAs as novel therapeutic targets to treat kidney injury and fibrosis. Am J Physiol Renal Physiol. 2016; 310(10): F931–F944.
  108. Chen HY, Zhong X, Huang XR, et al. MicroRNA-29b inhibits diabetic nephropathy in db/db mice. Mol Ther. 2014; 22(4): 842–853.
  109. Chen Y, Gao DY, Huang L. In vivo delivery of miRNAs for cancer therapy: Challenges and strategies. Adv Drug Deliv Rev. 2015; 81: 128–141.
  110. Li Z, Rana T. Therapeutic targeting of microRNAs: current status and future challenges. Nat Rev Drug Discov. 2014; 13(8): 622–638.
  111. Lanford RE, Hildebrandt-Eriksen ES, Petri A, et al. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science. 2010; 327(5962): 198–201.
  112. Simpson K, Wonnacott A, Fraser DJ, et al. MicroRNAs in Diabetic Nephropathy: From Biomarkers to Therapy. Curr Diab Rep. 2016; 16(3): 35.
  113. Hussain MdS, Gupta G, Samuel VP, et al. Immunopathology of herpes simplex virus-associated neuroinflammation: Unveiling the mysteries. Rev Med Virol. 2024; 34(1): e2491.
  114. Janssen HLA, Reesink HW, Lawitz EJ, et al. Treatment of HCV infection by targeting microRNA. N Engl J Med. 2013; 368(18): 1685–1694.
  115. van der Ree MH, Stelma F, Willemse SB, et al. Safety, tolerability, and antiviral effect of RG-101 in patients with chronic hepatitis C: a phase 1B, double-blind, randomised controlled trial. Lancet. 2017; 389(10070): 709–717.
  116. Kurreck J, Wyszko E, Gillen C, et al. Design of antisense oligonucleotides stabilized by locked nucleic acids. Nucleic Acids Res. 2002; 30(9): 1911–1918.
  117. Adams BD, Parsons C, Walker L, et al. Targeting noncoding RNAs in disease. J Clin Invest. 2017; 127(6): 761–771.
  118. Garitano-Trojaola A, Agirre X, Prósper F, et al. Long non-coding RNAs in haematological malignancies. Int J Mol Sci. 2013; 14(8): 15386–15422.
  119. Ji TT, Qi YH, Li XY, et al. Long noncoding RNA Gm6135 functions as a competitive endogenous RNA to regulate toll-like receptor 4 expression by sponging miR-203-3p in diabetic nephropathy. J Cell Physiol. 2019; 234(5): 6633–6641.
  120. Chen W, Peng R, Sun Y, et al. The topological key lncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathy via the miR‐449a/b/Trim11/Mek signaling pathway. FASEB J. 2019; 33(10): 11492–11506.
  121. Majumder S, Hadden MJ, Thieme K, et al. Dysregulated expression but redundant function of the long non-coding RNA HOTAIR in diabetic kidney disease. Diabetologia. 2019; 62(11): 2129–2142.
  122. Wang M, Wang S, Yao Di, et al. A novel long non-coding RNA CYP4B1-PS1-001 regulates proliferation and fibrosis in diabetic nephropathy. Mol Cell Endocrinol. 2016; 426: 136–145.
  123. Wang S, Chen X, Wang M, et al. Long Non-Coding RNA CYP4B1-PS1-001 Inhibits Proliferation and Fibrosis in Diabetic Nephropathy by Interacting with Nucleolin. Cell Physiol Biochem. 2018; 49(6): 2174–2187.
  124. Wang M, Yao Di, Wang S, et al. Long non-coding RNA ENSMUST00000147869 protects mesangial cells from proliferation and fibrosis induced by diabetic nephropathy. Endocrine. 2016; 54(1): 81–92.
  125. Zhang YY, Tang PMK, Tang PCT, et al. LRNA9884, a novel smad3-dependent long noncoding RNA, promotes diabetic kidney injury in db/db mice via enhancing MCP-1–dependent renal inflammation. Diabetes. 2019; 68(7): 1485–1498.
  126. Peng W, Huang S, Shen L, et al. Long noncoding RNA NONHSAG053901 promotes diabetic nephropathy via stimulating Egr-1/TGF-β-mediated renal inflammation. J Cell Physiol. 2019; 234(10): 18492–18503.
  127. Zhang P, Sun Y, Peng R, et al. Long non-coding RNA Rpph1 promotes inflammation and proliferation of mesangial cells in diabetic nephropathy via an interaction with Gal-3. Cell Death Dis. 2019; 10(7): 526.
  128. Xu J, Deng Y, Wang Yi, et al. SPAG5-AS1 inhibited autophagy and aggravated apoptosis of podocytes via SPAG5/AKT/mTOR pathway. Cell Prolif. 2020; 53(2): e12738.