Long Non-Coding RNA Small Nucleolar RNA Host Gene 5 (SNHG5) Regulates Renal Tubular Damage in Diabetic Nephropathy via Targeting MiR-26a-5p

Abstract

The study explored the diagnostic value of SNHG5 in diabetic nephropathy (DN) and investigated the role and mechanism on DN via establishing the in vitro HK2 cell model. This study recruited 62 types 2 diabetes mellitus (T2DM) patients, 58 DN patients and 60 healthy controls (HC). The expressions of serum SNHG5 and miR-26a-5p were measured by RT-qPCR analysis. The diagnostic value of SNHG5 in DN was assessed by ROC curve. The in vitro cell model was built to estimate the effects of SNHG5 on cell viability, cell apoptosis, inflammation response and oxidative stress. Serum SNHG5 was increased in DN patients (relative expression: 2.04±0.34) and had the diagnostic value in DN. After HK2 cells were treated with high glucose, the cell viability decreased and apoptosis increased, and the production of inflammatory cytokines and ROS enhanced significantly. It was noticed that inhibition of SNHG5 could reverse the above phenomenon caused by high glucose. Besides, serum miR-26a-5p was diminished in DN patients, and luciferase reporter gene revealed that miR-26a-5p is direct target of SNHG5. These results indicated that inhibition of SNHG5 may mitigate HG-induced renal tubular damage via targeting miR-26a-5p, which providing a new insight into the mechanism of renal tubule damage in DN patients.

Key words

SNHG5 - miR-26a-5p - diabetic nephropathy - diagnosis

• References

• 1 Kanwar YS, Sun L, Xie P. et al A glimpse of various pathogenetic mechanisms of diabetic nephropathy. Annu Rev Pathol 2011; 6: 395-423
• 2 Wang Y, He Z, Yang Q. et al XBP1 inhibits mesangial cell apoptosis in response to oxidative stress via the PTEN/AKT pathway in diabetic nephropathy. FEBS Open Bio 2019; 9: 1249-1258
• 3 Hu HC, Zheng LT, Yin HY. et al A significant association between rhein and diabetic nephropathy in animals: A systematic review and meta-analysis. Front Pharmacol 2019; 10: 1473
• 4 Ma X, Lu C, Lv C. et al The expression of miR-192 and its significance in diabetic nephropathy patients with different urine albumin creatinine ratio. J Diabetes Res 2016; 2016: 6789402
• 5 Zeni L, Norden AGW, Cancarini G. et al A more tubulocentric view of diabetic kidney disease. J Nephrol 2017; 30: 701-717
• 6 Ye S, Sun B, Wu W. et al LINC01123 facilitates proliferation, invasion and chemoresistance of colon cancer cells. Biosci Rep 2020; 40: BSR20194062
• 7 Zhang C, Ma MH, Liang Y. et al Novel long non-coding RNA LINC02532 promotes gastric cancer cell proliferation, migration, and invasion in vitro. World J Gastrointest Oncol 2019; 11: 91-101
• 8 Hanson RL, Craig DW, Millis MP. et al Identification of PVT1 as a candidate gene for end-stage renal disease in type 2 diabetes using a pooling-based genome-wide single nucleotide polymorphism association study. Diabetes 2007; 56: 975-983
• 9 Millis MP, Bowen D, Kingsley C. et al Variants in the plasmacytoma variant translocation gene (PVT1) are associated with end-stage renal disease attributed to type 1 diabetes. Diabetes 2007; 56: 3027-3032
• 10 Xie C, Wu W, Tang A. et al lncRNA GAS5/miR-452-5p reduces oxidative stress and pyroptosis of high-glucose-stimulated renal tubular cells. Diabetes Metab Syndr Obes 2019; 12: 2609-2617
• 11 Shen Q, Zheng J, Wang X. et al LncRNA SNHG5 regulates cell apoptosis and inflammation by miR-132/PTEN axis in COPD. Biomed Pharmacother 2020; 126: 110016
• 12 Li X, Liu L, Luo Y. et al Long non-coding RNA SNHG5 promotes glioma progression via miR-205/E2F3 axis. Biosci Rep 2019; 39: BSR20190668
• 13 Wei W, Tian H, Fu X. et al Long non-coding RNA (lncRNA) SNHG5 participates in vertical sleeve gastrectomy for type II diabetes mellitus by regulating TGR5. Med Sci Monit 2020; 26: e920628
• 14 Wang M, Wei J, Shang F. et al Down-regulation of lncRNA SNHG5 relieves sepsis-induced acute kidney injury by regulating the miR-374a-3p/TLR4/NF-kappaB pathway. J Biochem 2021; 169: 575-583
• 15 American Diabetes A Standards of medical care in diabetes-2017 abridged for primary care providers. Clin Diabetes 2017; 35: 5-26
• 16 Tervaert TW, Mooyaart AL, Amann K. et al Pathologic classification of diabetic nephropathy. J Am Soc Nephrol 2010; 21: 556-563
• 17 Papadopoulou-Marketou N, Chrousos GP, Kanaka-Gantenbein C. Diabetic nephropathy in type 1 diabetes: a review of early natural history, pathogenesis, and diagnosis. Diabetes Metab Res Rev 2017; 33 Epub 2016 Oct 4
• 18 Feng H, Gu J, Gou F. et al High glucose and lipopolysaccharide prime NLRP3 inflammasome via ROS/TXNIP pathway in mesangial cells. J Diabetes Res 2016; 6973175
• 19 Chi JR, Yu ZH, Liu BW. et al SNHG5 promotes breast cancer proliferation by sponging the miR-154-5p/PCNA axis. Mol Ther Nucleic Acids 2019; 17: 138-149
• 20 Wei S, Sun S, Zhou X. et al SNHG5 inhibits the progression of EMT through the ubiquitin-degradation of MTA2 in oesophageal cancer. Carcinogenesis 2021; 42: 315-326
• 21 Vallon V, Thomson SC. Renal function in diabetic disease models: the tubular system in the pathophysiology of the diabetic kidney. Annu Rev Physiol 2012; 74: 351-375
• 22 Gilbert RE. Proximal tubulopathy: prime mover and key therapeutic target in diabetic kidney disease. Diabetes 2017; 66: 791-800
• 23 Bernardo-Bermejo S, Sanchez-Lopez E, Castro-Puyana M. et al A non-targeted capillary electrophoresis-mass spectrometry strategy to study metabolic differences in an in vitro model of high-glucose induced changes in human proximal tubular HK-2 cells. Molecules 2020; 25: 512
• 24 Tang SC, Lai KN. The pathogenic role of the renal proximal tubular cell in diabetic nephropathy. Nephrol Dial Transplant 2012; 27: 3049-3056
• 25 Kumar D, Robertson S, Burns KD. Evidence of apoptosis in human diabetic kidney. Mol Cell Biochem 2004; 259: 67-70
• 26 Larriba E, del Mazo J. Role of non-coding RNAs in the transgenerational epigenetic transmission of the effects of reprotoxicants. Int J Mol Sci 2016; 17: 452
• 27 Gao J, Zeng K, Liu Y. et al LncRNA SNHG5 promotes growth and invasion in melanoma by regulating the miR-26a-5p/TRPC3 pathway. Onco Targets Ther 2019; 12: 169-179
• 28 Yang Y, Xi L, Ma Y. et al The lncRNA small nucleolar RNA host gene 5 regulates trophoblast cell proliferation, invasion, and migration via modulating miR-26a-5p/N-cadherin axis. J Cell Biochem 2019; 120: 3173-3184
• 29 Gholaminejad A, Abdul Tehrani H, Gholami Fesharaki M. Identification of candidate microRNA biomarkers in diabetic nephropathy: A meta-analysis of profiling studies. J Nephrol 2018; 31: 813-831
• 30 Duan Y, Luo Q, Wang Y. et al Adipose mesenchymal stem cell-derived extracellular vesicles containing microRNA-26a-5p target TLR4 and protect against diabetic nephropathy. J Biol Chem 2020; 295: 12868-12884