title: Circulating microRNA profiles and the identification of miR-593 and miR-511 which directly target the PROP1 gene in children with combined pituitary hormone deficiency.
abstract: Since the tissue of children with combined pituitary hormone deficiency (CPHD) is not readily accessible, a new focus in children with CPHD is the blood-based expression profiling of non-protein coding genes, such as microRNAs (miRNAs or miRs), which regulate gene expression by inhibiting the translation of mRNAs. In this study, to address this, we identified potential miRNA signatures for CPHD by comparing genome-wide miRNA expression profiles in the serum of children with CPHD vs. normal (healthy) controls. Human embryonic kidney 293T cells were transfected with miR-593 or miR-511 oligonucleotides. Potential target gene expression was validated by western blot analysis for proteins and by miR-593 or miR-511 reporter assay using PROP1 gene 3'-untranslated region (3'-UTR) reporter. The miR-593 and miR-511 levels in the serum of 103 children with CPHD were assessed using the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) method. We found 23 upregulated and 19 downregulated miRNAs with abnormal expression in children with CPHD compared with the normal controls using miRNA microarray analysis and RT-qPCR. miR-593 and miR-511 targeted the 3'-UTR of the PROP1 gene and attenuated the expression of PROP1. The levels of miR-593 and miR-511 in the serum of children with CPHD were increased compared with those in the control subjects. According to Youden's index, the sensitivity was 82.54 and 84.86%, and the specificity was 98.15 and 91.36% for miR-593 and miR-511, respectively. The various levels of specific miRNAs, particularly miR-593 and miR-511 whose direct target is the PROP1 gene, may serve as a non-invasive diagnostic biomarkers for children with CPHD.
authors.affiliation: Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Zengmin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Fengxue
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Guimei
authors.initials: G
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions; D000015:Abnormalities, Multiple / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D019066:Facies; D005260:Female; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010908:Pituitary Hormones, Anterior / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D050817:Transcription Factor Pit-1 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D015415:Biomarkers; D018398:Homeodomain Proteins; C578471:MIRN511 microRNA, human; C577650:MIRN593 microRNA, human; D035683:MicroRNAs; D010908:Pituitary Hormones, Anterior; C102134:Prophet of Pit-1 protein; D050817:Transcription Factor Pit-1