MiR-192–5p targets cell cycle regulation in diabetic kidney disease via cyclin-dependent kinase inhibitor 3
Diabetic kidney disease (DKD), a.k.a diabetic nephropathy, is a leading cause of end-stage renal disease. However, in a fair percentage of patients with type-2 diabetes, renal involvement also occurs due to non-diabetic reasons (non-diabetic kidney disease, NDKD). In this study, we identified miRNA-...
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KeAi Communications Co., Ltd.
2025-04-01
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| Series: | Non-coding RNA Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468054024001549 |
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| author | Biswajit Sahoo Deendayal Das Mishra Swasti Tiwari |
| author_facet | Biswajit Sahoo Deendayal Das Mishra Swasti Tiwari |
| author_sort | Biswajit Sahoo |
| collection | DOAJ |
| description | Diabetic kidney disease (DKD), a.k.a diabetic nephropathy, is a leading cause of end-stage renal disease. However, in a fair percentage of patients with type-2 diabetes, renal involvement also occurs due to non-diabetic reasons (non-diabetic kidney disease, NDKD). In this study, we identified miRNA-mRNA regulatory networks specific to human DKD pathogenesis. miRNA profiling of the renal biopsy from cases (DKD, n = 5), disease controls (T2DM with NDKD, n = 6), and non-diabetic, non-CKD controls (patients undergoing nephrectomy for renal cancer, n = 3) revealed 68 DKD-specific miRNA regulation. Sixteen target mRNAs of these DKD-miRNAs were found to have a negative association with the estimated glomerular filtration rate (eGFR) in patients with DKD. The renal gene expression and eGFR data of DKD patients (n = 10–18) in the NephroSeq database were used. Based on these findings, 11 miRNA-mRNA regulatory networks were constructed for human DKD pathogenesis. Of these, in-vitro validation of miR-192-5p- CDKN3 (Cell cycle-dependent kinase inhibitor 3) network was done as miR-192–5p exhibited a maximum number of target genes in the identified DKD regulatory networks, and CDKN3 appeared as a novel target of miR-192–5p in our study. We demonstrated that miR-192–5p overexpression or knockdown of CDKN3 attenuated high glucose-induced apoptosis, fibrotic gene expression, cell hypertrophy, and cell cycle dysregulation and improved viability of proximal tubular cells. Moreover, miR-192–5p overexpression significantly inhibited CDKN3 mRNA and protein expression in proximal tubular cells. Overall, 11 miRNA-mRNA regulatory networks were predicted for human DKD pathogenesis; among these, the association of miR-192-5p- CDKN3 network DKD pathogenesis was confirmed in proximal tubular cell culture. |
| format | Article |
| id | doaj-art-93709ba8701a4ae88b075133e9a3c310 |
| institution | OA Journals |
| issn | 2468-0540 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | KeAi Communications Co., Ltd. |
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| series | Non-coding RNA Research |
| spelling | doaj-art-93709ba8701a4ae88b075133e9a3c3102025-08-20T02:13:07ZengKeAi Communications Co., Ltd.Non-coding RNA Research2468-05402025-04-0111607210.1016/j.ncrna.2024.11.003MiR-192–5p targets cell cycle regulation in diabetic kidney disease via cyclin-dependent kinase inhibitor 3Biswajit Sahoo0Deendayal Das Mishra1Swasti Tiwari2Department of Molecular Medicine & Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, IndiaDepartment of Molecular Medicine & Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, IndiaCorresponding author.; Department of Molecular Medicine & Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, IndiaDiabetic kidney disease (DKD), a.k.a diabetic nephropathy, is a leading cause of end-stage renal disease. However, in a fair percentage of patients with type-2 diabetes, renal involvement also occurs due to non-diabetic reasons (non-diabetic kidney disease, NDKD). In this study, we identified miRNA-mRNA regulatory networks specific to human DKD pathogenesis. miRNA profiling of the renal biopsy from cases (DKD, n = 5), disease controls (T2DM with NDKD, n = 6), and non-diabetic, non-CKD controls (patients undergoing nephrectomy for renal cancer, n = 3) revealed 68 DKD-specific miRNA regulation. Sixteen target mRNAs of these DKD-miRNAs were found to have a negative association with the estimated glomerular filtration rate (eGFR) in patients with DKD. The renal gene expression and eGFR data of DKD patients (n = 10–18) in the NephroSeq database were used. Based on these findings, 11 miRNA-mRNA regulatory networks were constructed for human DKD pathogenesis. Of these, in-vitro validation of miR-192-5p- CDKN3 (Cell cycle-dependent kinase inhibitor 3) network was done as miR-192–5p exhibited a maximum number of target genes in the identified DKD regulatory networks, and CDKN3 appeared as a novel target of miR-192–5p in our study. We demonstrated that miR-192–5p overexpression or knockdown of CDKN3 attenuated high glucose-induced apoptosis, fibrotic gene expression, cell hypertrophy, and cell cycle dysregulation and improved viability of proximal tubular cells. Moreover, miR-192–5p overexpression significantly inhibited CDKN3 mRNA and protein expression in proximal tubular cells. Overall, 11 miRNA-mRNA regulatory networks were predicted for human DKD pathogenesis; among these, the association of miR-192-5p- CDKN3 network DKD pathogenesis was confirmed in proximal tubular cell culture.http://www.sciencedirect.com/science/article/pii/S2468054024001549Diabetic kidney diseasemiRNA-mRNA regulatory networksDiabetic nephropathyHigh glucoseCell cycle-dependent kinase inhibitor |
| spellingShingle | Biswajit Sahoo Deendayal Das Mishra Swasti Tiwari MiR-192–5p targets cell cycle regulation in diabetic kidney disease via cyclin-dependent kinase inhibitor 3 Non-coding RNA Research Diabetic kidney disease miRNA-mRNA regulatory networks Diabetic nephropathy High glucose Cell cycle-dependent kinase inhibitor |
| title | MiR-192–5p targets cell cycle regulation in diabetic kidney disease via cyclin-dependent kinase inhibitor 3 |
| title_full | MiR-192–5p targets cell cycle regulation in diabetic kidney disease via cyclin-dependent kinase inhibitor 3 |
| title_fullStr | MiR-192–5p targets cell cycle regulation in diabetic kidney disease via cyclin-dependent kinase inhibitor 3 |
| title_full_unstemmed | MiR-192–5p targets cell cycle regulation in diabetic kidney disease via cyclin-dependent kinase inhibitor 3 |
| title_short | MiR-192–5p targets cell cycle regulation in diabetic kidney disease via cyclin-dependent kinase inhibitor 3 |
| title_sort | mir 192 5p targets cell cycle regulation in diabetic kidney disease via cyclin dependent kinase inhibitor 3 |
| topic | Diabetic kidney disease miRNA-mRNA regulatory networks Diabetic nephropathy High glucose Cell cycle-dependent kinase inhibitor |
| url | http://www.sciencedirect.com/science/article/pii/S2468054024001549 |
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