The expression of Drosha, DGCR8, Dicer and Ago-2 genes are upregulated in human umbilical vein endothelial cells under hyperglycemic condition

Open access


Objectives. It has been shown that dysregulation of miRNAs expression contributes to the pathogenesis and progression of the diabetes and diabetes-related complications. Drosha, DGCR8, Dicer, and Ago-2 are involved in the miRNA maturation. The aim of the present study was to investigate the mRNA expression levels of these genes in the human umbilical vein endothelial cells (HUVECs) under hyperglycemic condition.

Methods. HUVECs were cultured in normo-(5 mM) and hyperglycemic (25 mM) conditions for 24 h. As osmotic control, cells were treated with D-mannitol (25 mM, for 24 h). The mRNA expression levels of Drosha, DGCR8, Dicer and Ago-2 were evaluated using quantitative real-time PCR.

Results. The expression level of Drosha, DGCR8, Dicer, and Ago-2 were increased in hyperglycemic HUVECs compared to the control group.

Conclusion. Our results show that under hyperglycemic condition, expression of genes involved in the miRNA maturation was significantly increased in HUVECs. Upregulation of these genes may have role in diabetic complications through the dysregulation of the miRNA expression.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • Aure MR Leivonen SK Fleischer T Zhu Q Overgaard J Alsner J Tramm T Louhimo R Alnæs GI Perala M Busato F Touleimat N Tost J Børresen-Dale AL Hautaniemi S Troyanskaya OG Lingjærde OC Sahlberg KK Kristensen VN. Individual and combined effects of DNA methylation and copy number alterations on miRNA expression in breast tumors. Genome Biol 14 R126 2013.

  • Bhattacharya S Aggarwal R Singh VP Ramachandran S Datta M. Downregulation of miRNAs during delayed wound healing in diabetes: Role of Dicer. Mol Med 2015.

  • Chavali V Tyagi SC Mishra PK. Differential expression of dicer miRNAs and inflammatory markers in diabetic Ins2+/− Akita hearts. Cell Biochem Biophys 68 25–35 2014.

  • Di Leva G Calin GA Croce CM. MicroRNAs: fundamental facts and involvement in human diseases. Birth Defects Res C Embryo Today 78 180–189 2006.

  • Fardmanesh H Shekari M Movafagh A Alizadeh Shargh S Poursadegh Zonouzi AA Shakerizadeh S Poursadegh Zonouzi A Hosseinzadeh A. Upregulation of the double-stranded RNA binding protein DGCR8 in invasive ductal breast carcinoma. Gene 581 146–151 2016.

  • Guay C Roggli E Nesca V Jacovetti C Regazzi R. Diabetes mellitus a microRNA-related disease? Transl Res 157 253–264. 2011.

  • Guay C Regazzi R. Circulating microRNAs as novel biomarkers for diabetes mellitus. Nat Rev Endocrinol 9 513–521 2013.

  • Kalis M Bolmeson C Esguerra JL Gupta S Edlund A Tormo-Badia N Speidel D Holmberg D Mayans S Khoo NK Wendt A Eliasson L Cilio CM. Beta-cell specific deletion of Dicer1 leads to defective insulin secretion and diabetes mellitus. PLoS One 6 e29166 2011.

  • Kamali K Korjan ES Eftekhar E Malekzadeh K Soufi FG. The role of miR-146a on NF-κB expression level in human umbilical vein endothelial cells under hyperglycemic condition. Bratisl Lek Listy 117 376–380 2016.

  • Kantharidis P Wang B Carew RM Lan HY. Diabetes complications: the microRNA perspective. Diabetes 60 1832–1837 2011.

  • Kaspi H Pasvolsky R Hornstein E. Could microRNAs contribute to the maintenance of β cell identity? Trends Endocrinol Metab 25 285–292 2014.

  • Lin S Gregory RI. MicroRNA biogenesis pathways in cancer. Nat Rev Cancer 15 321–333 2015.

  • McClelland AD Kantharidis P. microRNA in the development of diabetic complications. Clin Sci (Lond) 126 95–110 2014.

  • Melkman-Zehavi T Oren R Kredo-Russo S Shapira T Mandelbaum AD Rivkin N Nir T Lennox KA Behlke MA Dor Y Hornstein E. miRNAs control insulin content in pancreatic β-cells via downregulation of transcriptional repressors. EMBO J 30 835–845 2011.

  • Park SY Jeong HJ Yang WM Lee W. Implications of microRNAs in the pathogenesis of diabetes. Arch Pharm Res 36 154–166 2013.

  • Rahimi G Jafari N Khodabakhsh M Shirzad Z Dogaheh HP. Upregulation of microRNA processing enzymes Drosha and Dicer in gestational diabetes mellitus. Gynecol Endocrinol 31 156–159 2015.

  • Tattikota SG Sury MD Rathjen T Wessels HH Pandey AK You X Becker C Chen W Selbach M Poy MN. Argonaute2 regulates the pancreatic β-cell secretome. Mol Cell Proteomics 12 1214–1225 2013.

  • Poursadegh Zonouzi AA Nejatizadeh A Rahmati-Yamchi M Fardmanesh H Shakerizadeh S Poursadegh Zonouzi A Nejati-Koshki K Shekari M. Dysregulated expression of Dicer in invasive ductal breast carcinoma. Med Oncol 32 203 2015.

Journal information
Impact Factor

CiteScore 2018: 1.27

SCImago Journal Rank (SJR) 2018: 0.411
Source Normalized Impact per Paper (SNIP) 2018: 0.441

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 575 239 20
PDF Downloads 374 129 7