title: miR-582-5p is upregulated in patients with active tuberculosis and inhibits apoptosis of monocytes by targeting FOXO1.
abstract: Macrophage apoptosis is a host innate defense mechanism against tuberculosis (TB). In this study, we found that percentage of apoptotic cells in peripheral blood monocytes from patients with active TB was lower than that from healthy controls (p<0.001). To understand whether microRNAs can modulate apoptosis of monocytes, we investigated differentially expressed microRNAs in patients with active TB. miR-582-5p was mainly expressed in monocytes and was upregulated in patients with active TB. The apoptotic percentage of THP-1 cells transfected with miR-582-5p mimics was significantly lower than those transfected with negative control of microRNA mimics (p<0.001), suggesting that miR-582-5p could inhibit apoptosis of monocytes. To our knowledge, the role of miR-582-5p in regulating apoptosis of monocytes has not been reported so far. Systematic bioinformatics analysis indicated that FOXO1 might be a target gene for miR-582-5p and its 3'UTR contains potential binding sites for miR-582-5p. To determine whether miR-582-5p could influence FOXO1 expression, miR-582-5p mimics or negative control of microRNA mimics were transfected into THP-1 cells. RT-PCR and western blot analysis showed that the miR-582-5p could suppress both FOXO1 mRNA and protein expression. Co-transfection of miR-582-5p and FOXO1 3'UTR-luciferase reporter vector into cells demonstrated that significant decrease in luciferase activity was only found in reporter vector that contained a wild type sequence of FOXO1 3'UTR, suggesting that miR-582-5p could directly target FOXO1. In conclusion, miR-582-5p inhibited apoptosis of monocytes by down-regulating FOXO1 expression and might play an important role in regulating anti-M. tuberculosis directed immune responses.
authors.affiliation: Division of Research, Laboratory of Tuberculosis Prevention and Treatment of PLA, Institute of Tuberculosis, 309 Hospital, Beijing, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.forename: Xinjing
authors.initials: X
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Zhai
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Cheng
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D017209:Apoptosis / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009000:Monocytes / Q000378:metabolism*; D014162:Transfection / Q000379:methods; D014376:Tuberculosis / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C000593706:MIRN582 microRNA, human; D035683:MicroRNAs