title: Role of microRNA-214-targeting phosphatase and tensin homolog in advanced glycation end product-induced apoptosis delay in monocytes.
abstract: Advanced glycation end products (AGEs) delay spontaneous apoptosis of monocytes and contribute to the development of inflammatory responses. However, the mechanism by which AGEs affect monocyte apoptosis is unclear. We studied the role of microRNA-214 (miR-214) and its target gene in AGE-induced monocytic apoptosis delay. Using microRNA (miRNA) microarray and stem-loop, quantitative RT-PCR assay, we studied genome-wide miRNA expression in THP-1 cells treated with or without AGEs. Significant upregulation of miR-214 was consistently observed in THP-1 and human monocytes treated with various AGEs, and AGE-induced monocytic miR-214 upregulation was likely through activation of receptor for AGEs. A striking increase in miR-214 was also detected in monocytes from patients with chronic renal failure. Luciferase reporter assay showed that miR-214 specifically binds to the phosphatase and tensin homolog (PTEN) mRNA 3'-untranslated region, implicating PTEN as a target gene of miR-214. PTEN expression is inversely correlated with miR-214 level in monocytes. Compared with normal monocytes, AGE-treated monocytes and monocytes from chronic renal failure patients exhibited lower PTEN levels and delayed apoptosis. Overexpression of pre-miR-214 led to impaired PTEN expression and delayed apoptosis of THP-1 cells, whereas knockdown of miR-214 level largely abolished AGE-induced cell survival. Our findings define a new role for miR-214-targeting PTEN in AGE-induced monocyte survival.
authors.affiliation: Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Jiangsu 210093, China
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Li
authors.forename: Dong-Xia
authors.initials: DX
authors.lastname: Hou
authors.forename: Ya-Lan
authors.initials: YL
authors.lastname: Guo
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Yang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology; D018390:Gene Targeting; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference / Q000276:immunology; D012709:Serum Albumin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000075462:Serum Albumin, Human; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D017127:Glycation End Products, Advanced; C547397:MIRN214 microRNA, human; D035683:MicroRNAs; D012709:Serum Albumin; D025521:Tumor Suppressor Proteins; C109748:advanced glycation end products-human serum albumin; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D000075462:Serum Albumin, Human