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pmid:31557418
Elevated hsa-miR-590-3p expression down-regulates HMGB2 expression and contributes to the severity of IgA nephropathy.
Yaling Zhai · Yuanyuan Qi · Xiaoqing Long · Yanna Dou · Dong Liu · Genyang Cheng · Jing Xiao · Zhangsuo Liu · Zhanzheng Zhao
Journal of cellular and molecular medicine · 2019 doi:10.1111/jcmm.14582
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Complete file
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Our study aimed to provide a deep understanding of IgAN and focused on the dysregulation of hsa-miR-590-3p and its target gene HMGB2 in PBMCs. Three gene expression profile datasets (GSE14795, GSE73953 and GSE25590) were downloaded from the GEO database. The DEGs (differentially expressed genes)-miRNA network that was associated with IgAN was constructed by Cytoscape, and HMGB2 and hsa-miR-590-3p were selected for further exploration. The dual-luciferase reporter system was utilized to verify their interaction. Then, the expression levels of HMGB2 and hsa-miR-590-3p in PBMCs were detected by qPCR in another cohort, and the correlation of their expression levels with the clinical pathological manifestations and serum Gd-IgA1(galactose-deficient IgA1) levels was also investigated. HMGB2 was identified as the target gene of hsa-miR-590-3p. Furtherly, the elderly patients had higher HMGB2 expression levels than the expression levels of the younger patients. As the serum creatinine, serum BUN levels increased, the expression of HMGB2 decreased; Besides, the HMGB2 expression was positively correlated with serum complement 3(C3) levels, and it also had a negative correlation with the diastolic blood pressure, but not reach statistical significance. What is more, both hsa-miR-590-3p and HMGB2 expression had a slight correlation tendency with serum Gd-IgA1 levels in the whole population. In conclusion, HMGB2, the target gene of hsa-miR-590-3p, was identified to correlate with the severity of IgAN, and this provides more clues for the pathogenesis of IgAN.", "claims": [{"id": "claim-method", "statement": "For continuous variables, data with normal distribution were expressed as the mean ± SD and were compared by an independent‐sample t test, and Pearson Correlation was used if need; the other data were expressed as the median (first quartile and third quartile) and were analysed by the Mann‐Whitney U test, and the Spearman Correlation was utilized for the correlation analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31557418", "locator": "sections[10] \"Statistical analysis\" paragraph 2", "quote": "For continuous variables, data with normal distribution were expressed as the mean ± SD and were compared by an independent‐sample t test, and Pearson Correlation was used if need; the other data were expressed as the median (first quartile and third quartile) and were analysed by the Mann‐Whitney U test, and the Spearman Correlation was utilized for the correlation analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Raw data used during the current study are available from the corresponding author on reasonable request for non‐commercial use.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31557418", "locator": "sections[23] \"(untitled)\" paragraph 1", "quote": "Raw data used during the current study are available from the corresponding author on reasonable request for non‐commercial use."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:31557418"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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"hsa‐miR‐384"]], "row_count": 20, "column_count": 3, "numeric_cells": 40, "header_rows": 1, "locator": "section[12]/table-wrap[1]#jcmm14582-tbl-0003"}}, {"id": "asset:table:pmid:31557418:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:0dbdad815c91c7194252ed134695ff3abcfb4cd61fc815701a0cac8a8b292c5d", "bytes": 3796, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[2]#jcmm14582-tbl-0004", "version": null, "note": "GO and KEGG enrichment analysis results for DEGs identified in the three microarray", "structure": {"pmcid": "PMC6815813", "section_index": 12, "section_title": "Screened miRNAs and target genes associated with IgAN", "row_count": 30, "column_count": 4}, "table": {"label": "Table 4", "caption": "GO and KEGG enrichment analysis results for DEGs identified in the three microarray", "rows": [["Description", "gene count", "Pvalue", "Genes"], ["GO terms"], ["GO:0044699‐single‐organism process", "18", "1.00 × 10‐3", "ZFR;TMEM57;MAN1A1;HABP4;IFIT5;TGFA;CETN3;GCC2;JMJD1C;NAMPT;RASA1;MAPK6;RAB1A;ARID4A;TUBGCP3;HMGB2;NPTN;CNOT3"], ["GO:0044707‐single‐multicellular organism process", "13", "4.07 × 10‐6", "ZFR;TMEM5;HABP4;TGFA;JMJD1C;NAMPT;RASA1;MAPK6;RAB1A;ARID4A;HMGB2;NPTN;CNOT3"], ["GO:0032501‐multicellular organismal process", "13", "7.82 × 10‐6", "ZFR;TMEM57;HABP4;TGFA;JMJD1C;NAMPT;RASA1;MAPK6 ;RAB1A;ARID4A;HMGB2;NPTN;CNOT3"], ["GO:0048856‐anatomical structure development", "11", "5.60 × 10‐5", "ZFR;TMEM57;;NAMPT;RASA1;MAPK6 ;RAB1A;ARID4A;HMGB2;NPTN;CNOT3"], ["GO:0044767‐single‐organism developmental process", "11", "1.13 × 10‐4", "ZFR;TMEM57;TGFA;NAMPT;RASA1;MAPK6 ;RAB1A;ARID4A;HMGB2;NPTN;CNOT3"], ["GO:0032502‐developmental process", "11", "1.32 × 10‐4", "ZFR;TMEM57;TGFA;NAMPT;RASA1;MAPK6 ;RAB1A;ARID4A;HMGB2;NPTN;CNOT3"], ["GO:0060255‐regulation of macromolecule metabolic process", "11", "1.57 × 10‐3", "HABP4;TGFA;JMJD1C;NAMPT;RASA1;MAPK6 ;RAB1A;ARID4A;HMGB2;NPTN;CNOT3"], ["GO:0019222‐regulation of metabolic process", "11", "6.12 × 10‐3", "HABP4;TGFA;JMJD1C;NAMPT;RASA1;MAPK6 ;RAB1A;ARID4A;HMGB2;NPTN;CNOT3"], ["GO:0007275‐multicellular organism development", "10", "1.02 × 10‐4", "ZFR;TMEM57;TGFA;NAMPT;RASA1;MAPK6 ;ARID4A;HMGB2;NPTN;CNOT3"], ["GO:0048518‐positive regulation of biological process", "10", "5.60 × 10‐4", "IFIT5;TGFA;NAMPT;RASA1;MAPK6 ;RAB1A;ARID4A;HMGB2;NPTN;CNOT3"], ["GO:0016043‐cellular component organization", "10", "5.45 × 10‐3", "CETN3;GCC2;JMJD1C;RASA1;MAPK6 ;RAB1A;ARID4A;TUBGCP3;HMGB2;NPTN"], ["GO:0080090‐regulation of primary metabolic process", "10", "6.26 × 10‐3", "HABP4;TGFA;JMJD1C;NAMPT;RASA1;RAB1A;ARID4A;HMGB2;NPTN;CNOT3"], ["GO:0071840‐cellular component organization or biogenesis", "10", "6.85 × 10‐3", "CETN3;GCC2;JMJD1C;RASA1;MAPK6 ;RAB1A;ARID4A;TUBGCP3;HMGB2;NPTN"], ["GO:0031323‐regulation of cellular metabolic process", "10", "6.93 × 10‐3", "HABP4;TGFA;JMJD1C;NAMPT;RASA1;RAB1A;ARID4A;HMGB2;NPTN;CNOT3"], ["GO:0048522‐positive regulation of cellular process", "9", "5.74 × 10‐4", "IFIT5;TGFA;NAMPT;MAPK6 ;RAB1A;ARID4A;HMGB2;NPTN;CNOT3"], ["GO:0048731‐system development", "8", "1.59 × 10‐3", "TMEM57;TGFA;NAMPT;RASA1;MAPK6 ;ARID4A;HMGB2;NPTN"], ["GO:0006996‐organelle organization", "8", "4.66 × 10‐3", "CETN3;GCC2;JMJD1C;RASA1;RAB1A;ARID4A;TUBGCP3;HMGB2"], ["GO:0006464‐cellular protein modification process", "8", "9.25 × 10‐3", "MAN1A1;TGFA;JMJD1C;RASA1;MAPK6 ;RAB1A;ARID4A;NPTN"], ["GO:0036211‐protein modification process", "8", "9.25 × 10‐3", "MAN1A1;TGFA;JMJD1C;RASA1;MAPK6 ;RAB1A;ARID4A;NPTN"], ["GO:0048468‐cell development", "7", "9.85 × 10‐5", "RASA1;MAPK6 ;RAB1A;ARID4A;HMGB2;NPTN;CNOT3"], ["GO:1902589‐single‐organism organelle organization", "7", "2.16 × 10‐3", "CETN3;GCC2;RASA1;RAB1A;ARID4A;TUBGCP3;HMGB2"], ["GO:0009893‐positive regulation of metabolic process", "7", "3.75 × 10‐3", "TGFA;NAMPT;RASA1;RAB1A;ARID4A;HMGB2;NPTN"], ["GO:0030154‐cell differentiation", "7", "3.83 × 10‐3", "RASA1;MAPK6 ;RAB1A;ARID4A;HMGB2;NPTN;CNOT3"], ["GO:0065008‐regulation of biological quality", "7", "4.32 × 10‐3", "HABP4;JMJD1C;RASA1;RAB1A;ARID4A;HMGB2;NPTN"], ["GO:0048869‐cellular developmental process", "7", "7.37 × 10‐3", "RASA1;MAPK6 ;RAB1A;ARID4A;HMGB2;NPTN;CNOT3"], ["KEGG pathways"], ["hsa00760‐Nicotinate and nicotinamide metabolism", "1", "2.94 × 10‐2", "NAMPT"], ["hsa00510‐N‐Glycan biosynthesis", "1", "4.76 × 10‐2", "MAN1A1"]], "row_count": 30, "column_count": 4, "numeric_cells": 88, "header_rows": 1, "locator": "section[12]/table-wrap[2]#jcmm14582-tbl-0004"}}, {"id": "asset:table:pmid:31557418:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:d2a17d262ad93785f2a518a62b962647246f8a52efdc4326a6bc5a7a6d428d93", "bytes": 980, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#jcmm14582-tbl-0005", "version": null, "note": "The baseline data of 37 patients with IgAN", "structure": {"pmcid": "PMC6815813", "section_index": 14, "section_title": "Increased hsa‐miR‐590‐3p expression and decreased HMGB2 expression in IgAN", "row_count": 22, "column_count": 2}, "table": {"label": "Table 5", "caption": "The baseline data of 37 patients with IgAN", "rows": [["Characters", "Mean ± SD or median(IQR) or n"], ["Male/female", "23/14"], ["Age (year)", "42.11 ± 14.80"], ["With hypertension (%)", "26(70.27%)"], ["SBP (mmHg)", "135.97 ± 17.61"], ["DBP (mmHg)", "86.00 ± 10.39"], ["24 h proteinuria (g/d)", "1.75 (0.75,4.09)"], ["SCR (μmol/L)", "117 (82,189.50)"], ["BUN (mmol/L)", "6.60 (5.00,11.61)"], ["Uric Acid (μmol/L)", "342.19 ± 82.37"], ["Albumin (g/L)", "35.23 ± 8.98"], ["TCHO (mmol/L)", "4.40 (3.59,5.43)"], ["TG (mmol/L)", "1.93 (1.17, 2.60)"], ["C3 (mg/L)", "1.21 (1.04,1.38)"], ["C4 (mg/L)", "0.30 (0.25, 0.34)"], 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