LncRNA SNHG16 Aggravates High Glucose-Induced Podocytes Injury in Diabetic Nephropathy Through Targeting MiR-106a and Thereby Up-Regulating KLF9

Overview

Journal Diabetes Metab Syndr Obes

Publisher Dove Medical Press

Specialty Endocrinology

Date 2020 Oct 29

PMID 33116706

Citations 13

Authors

Xin He

XiuYa Zeng

Affiliations

Soon will be listed here.

Abstract

Introduction: Diabetic nephropathy (DN) is one of the major complications of diabetes and podocyte injury plays an important role in the DN pathogenesis. MicroRNA (miR)-106a is predicated to be a target of long noncoding RNA (lncRNA) SNHG16 and has been identified as a therapeutic biomarker for diabetic kidney diseases. However, the role of SNHG16/miR-106a axis in DN has not been illustrated. This study aimed to investigate whether SNHG16 could regulate podocyte injury via miR-106a in DN and uncover the underlying mechanism.

Methods: MPC5 podocytes were treated with control or high glucose (HG) medium, and then miR-106a level was measured. MPC5 cells that exposed to HG were overexpressed with miR-106a or not, following by overexpression with or without KLF9 or SNHG16. Then, cell viability, apoptosis, reactive oxygen species and the protein expression of synaptopodin and podocin were evaluated.

Results: MiR-106a was down-regulated in the serum of DN patients and HG-induced MPC5 podocytes. Overexpression of miR-106a suppressed HG-induced decrease in cell viability, Bcl-2, synaptopodin and podocin expression, increase in ROS, apoptotic cells, Bax and cleaved-caspase 3 expression. MiR-106a could bind to both KLF9 and lncRNA SNHG16, which were up-regulated in the serum of DN patients and HG-induced MPC5 podocytes. The level of miR-106a was decreased by SNHG16 overexpression and miR-106a overexpression reduced KLF9 expression. Furthermore, overexpression of KLF9 or SNHG16 blunted the protective effects of miR-106a on HG-induced MPC5 injury.

Discussion: LncRNA SNHG16 could promote HG-stimulated podocytes injury via targeting miR-106a to enhance KLF9 expression. The intervention of SNHG16/miR-106a/KLF9 may be a therapeutic treatment for DN.

Citing Articles

The Role of Antioxidant Transcription Factor Nrf2 and Its Activating Compounds in Systemic Lupus Erythematosus.

Liu L, de Leeuw K, Goor H, Westra J Antioxidants (Basel). 2024; 13(10).

PMID: 39456477 PMC: 11504041. DOI: 10.3390/antiox13101224.

STAT3-induced upregulation of lncRNA TTN-AS1 aggravates podocyte injury in diabetic nephropathy by promoting oxidative stress.

Wang W, Li Y, Zhu F, Huang Y Toxicol Res (Camb). 2024; 13(3):tfae079.

PMID: 38828128 PMC: 11142850. DOI: 10.1093/toxres/tfae079.

Downregulating lncRNA MIAT attenuates apoptosis of podocytes exposed to high glucose.

Xia J, Huang Y, Ma M, Liu F, Cao B Acta Diabetol. 2023; 61(4):451-460.

PMID: 38072843 DOI: 10.1007/s00592-023-02213-w.

Analysis of potential biomarkers for diabetic kidney disease based on single-cell RNA-sequencing integrated with a single-cell sequencing assay for transposase-accessible chromatin.

Shi Y, Guo Z, Liu F, Pan S, Gao D, Zhou S Aging (Albany NY). 2023; 15(19):10681-10704.

PMID: 37827693 PMC: 10599739. DOI: 10.18632/aging.205107.

Oxidative stress and inflammation in diabetic nephropathy: role of polyphenols.

Jin Q, Liu T, Qiao Y, Liu D, Yang L, Mao H Front Immunol. 2023; 14:1185317.

PMID: 37545494 PMC: 10401049. DOI: 10.3389/fimmu.2023.1185317.

References

Gholaminejad A, Tehrani H, Fesharaki M . Identification of candidate microRNA biomarkers in diabetic nephropathy: a meta-analysis of profiling studies. J Nephrol. 2018; 31(6):813-831. DOI: 10.1007/s40620-018-0511-5. View

Pan Y, Wei L, Wu X, Huo F, Mou J, Pei D . MiR-106a-5p inhibits the cell migration and invasion of renal cell carcinoma through targeting PAK5. Cell Death Dis. 2017; 8(10):e3155. PMC: 5680926. DOI: 10.1038/cddis.2017.561. View

Liu D, Zhang J, Liu F, Wang X, Pan S, Jiang D . Silencing of long noncoding RNA PVT1 inhibits podocyte damage and apoptosis in diabetic nephropathy by upregulating FOXA1. Exp Mol Med. 2019; 51(8):1-15. PMC: 6802617. DOI: 10.1038/s12276-019-0259-6. View

Tagawa A, Yasuda M, Kume S, Yamahara K, Nakazawa J, Chin-Kanasaki M . Impaired Podocyte Autophagy Exacerbates Proteinuria in Diabetic Nephropathy. Diabetes. 2015; 65(3):755-67. DOI: 10.2337/db15-0473. View

Cui C, Cui Y, Fu Y, Ma S, Zhang S . Microarray analysis reveals gene and microRNA signatures in diabetic kidney disease. Mol Med Rep. 2017; 17(2):2161-2168. PMC: 5783455. DOI: 10.3892/mmr.2017.8177. View

Liu X, Zhang L, Zhu T, Zhang R, Wang S, Bao Y . Overexpression of miR-34c inhibits high glucose-induced apoptosis in podocytes by targeting Notch signaling pathways. Int J Clin Exp Pathol. 2015; 8(5):4525-34. PMC: 4503014. View

Han Y, Xu X, Tang C, Gao P, Chen X, Xiong X . Reactive oxygen species promote tubular injury in diabetic nephropathy: The role of the mitochondrial ros-txnip-nlrp3 biological axis. Redox Biol. 2018; 16:32-46. PMC: 5842313. DOI: 10.1016/j.redox.2018.02.013. View

Zhang H, Jiang L, Sun D, Li J, Tang J . MiR-139-5p: promising biomarker for cancer. Tumour Biol. 2015; 36(3):1355-65. DOI: 10.1007/s13277-015-3199-3. View

Bhattacharjee N, Barma S, Konwar N, Dewanjee S, Manna P . Mechanistic insight of diabetic nephropathy and its pharmacotherapeutic targets: An update. Eur J Pharmacol. 2016; 791:8-24. DOI: 10.1016/j.ejphar.2016.08.022. View

10.

Wu Y, Xu D, Zhu X, Yang G, Ren M . MiR-106a Associated with Diabetic Peripheral Neuropathy Through the Regulation of 12/15-LOX-meidiated Oxidative/Nitrative Stress. Curr Neurovasc Res. 2017; 14(2):117-124. DOI: 10.2174/1567202614666170404115912. View

11.

Zhong Z, Zhou F, Wang D, Wu M, Zhou W, Zou Y . Expression of KLF9 in pancreatic cancer and its effects on the invasion, migration, apoptosis, cell cycle distribution, and proliferation of pancreatic cancer cell lines. Oncol Rep. 2018; 40(6):3852-3860. DOI: 10.3892/or.2018.6760. View

12.

Long J, Badal S, Ye Z, Wang Y, Ayanga B, Galvan D . Long noncoding RNA Tug1 regulates mitochondrial bioenergetics in diabetic nephropathy. J Clin Invest. 2016; 126(11):4205-4218. PMC: 5096930. DOI: 10.1172/JCI87927. View

13.

Hao H, Xia G, Wang C, Zhong F, Liu L, Zhang D . miR-106a suppresses tumor cells death in colorectal cancer through targeting ATG7. Med Mol Morphol. 2016; 50(2):76-85. DOI: 10.1007/s00795-016-0150-7. View

14.

Wu J, Li M, Zhang Y . Long noncoding RNA HOXA-AS2 regulates the expression of SCN3A by sponging miR-106a in breast cancer. J Cell Biochem. 2019; 120(9):14465-14475. DOI: 10.1002/jcb.28706. View

15.

Dewanjee S, Bhattacharjee N . MicroRNA: A new generation therapeutic target in diabetic nephropathy. Biochem Pharmacol. 2018; 155:32-47. DOI: 10.1016/j.bcp.2018.06.017. View

16.

Platania C, Maisto R, Trotta M, DAmico M, Rossi S, Gesualdo C . Retinal and circulating miRNA expression patterns in diabetic retinopathy: An in silico and in vivo approach. Br J Pharmacol. 2019; 176(13):2179-2194. PMC: 6555853. DOI: 10.1111/bph.14665. View

17.

Shi B, Ma C, Liu G, Guo Y . MiR-106a directly targets LIMK1 to inhibit proliferation and EMT of oral carcinoma cells. Cell Mol Biol Lett. 2019; 24:1. PMC: 6402160. DOI: 10.1186/s11658-018-0127-8. View

18.

Zhong F, Chen H, Xie Y, Azeloglu E, Wei C, Zhang W . Protein S Protects against Podocyte Injury in Diabetic Nephropathy. J Am Soc Nephrol. 2018; 29(5):1397-1410. PMC: 5967770. DOI: 10.1681/ASN.2017030234. View

19.

Yan Q, He B, Hao G, Liu Z, Tang J, Fu Q . KLF9 aggravates ischemic injury in cardiomyocytes through augmenting oxidative stress. Life Sci. 2019; 233:116641. DOI: 10.1016/j.lfs.2019.116641. View

20.

Pan Y, Zhuang Y, Zheng J, Pei D . MiR-106a: Promising biomarker for cancer. Bioorg Med Chem Lett. 2016; 26(22):5373-5377. DOI: 10.1016/j.bmcl.2016.10.042. View