The clinical value of hsa-miR-190b-5p in peripheral blood of pediatric β-thalassemia and its regulation on BCL11A expression

Background The B cell CLL/lymphoma 11A (BCL11A) is a key regulator of hemoglobin switching in β-thalassemia (β-thal). Previous study has suggested that dysregulated microRNAs are involved in the regulation of BCL11A expression. The aim of this study was to investigate the clinical value of hsa-miR-1...

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Veröffentlicht in:PloS one 2023-10, Vol.18 (10), p.e0292031-e0292031
Hauptverfasser: Chen, Meihuan, Wang, Xinrui, Wang, Haiwei, Zhang, Min, Chen, Lingji, Chen, Hong, Pan, Yali, Zhang, Yanhong, Xu, Liangpu, Huang, Hailong
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container_issue 10
container_start_page e0292031
container_title PloS one
container_volume 18
creator Chen, Meihuan
Wang, Xinrui
Wang, Haiwei
Zhang, Min
Chen, Lingji
Chen, Hong
Pan, Yali
Zhang, Yanhong
Xu, Liangpu
Huang, Hailong
description Background The B cell CLL/lymphoma 11A (BCL11A) is a key regulator of hemoglobin switching in β-thalassemia (β-thal). Previous study has suggested that dysregulated microRNAs are involved in the regulation of BCL11A expression. The aim of this study was to investigate the clinical value of hsa-miR-190b-5p in β-thal, and to confirm the regulatory effect of hsa-miR-190b-5p on BCL11A expression. Methods The peripheral blood of 25 pediatric β-thal patients and 25 healthy controls were selected, and qRT-PCR was used to analyze the levels of hsa-miR-190b-5p and BCL11A mRNA. The relationship between hsa-miR-190b-5p expression and hematological parameters was assessed by Pearson’s correlation test. The diagnostic power of hsa-miR-190b-5p was evaluated by ROC curves analysis. The direct integration between hsa-miR-190b-5p and BCL11A 3’-UTR was confirmed by luciferase reporter assay. Results Hsa-miR-190b-5p expression in pediatric β-thal was upregulated, and negatively correlated with the MCH and HbA levels, but positively correlated with the HbF level. Hsa-miR-190b-5p showed a good diagnostic capability for pediatric β-thal equivalent to that of HbA2 (AUC: 0.760 vs. 0.758). Moreover, the levels of BCL11A mRNA in pediatric β-thal were decreased, and hsa-miR-190b-5p had a negative correlation with BCL11A mRNA expression (r = -0.403). BCL11A was a target gene of hsa-miR-190b-5p. The mRNA and protein levels of BCL11A were diminished by introduction of hsa-miR-190b-5p, whereas its expression was upregulated by knockdown of hsa-miR-190b-5p. Conclusions Hsa-miR-190b-5p expression was upregulated in pediatric β-thal and might be an effective diagnostic biomarker. BCL11A was negatively regulated by hsa-miR-190b-5p, which might provide new target for the treatment of pediatric β-thal.
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Francis</contributor><creatorcontrib>Chen, Meihuan ; Wang, Xinrui ; Wang, Haiwei ; Zhang, Min ; Chen, Lingji ; Chen, Hong ; Pan, Yali ; Zhang, Yanhong ; Xu, Liangpu ; Huang, Hailong ; Borgio, J. Francis</creatorcontrib><description>Background The B cell CLL/lymphoma 11A (BCL11A) is a key regulator of hemoglobin switching in β-thalassemia (β-thal). Previous study has suggested that dysregulated microRNAs are involved in the regulation of BCL11A expression. The aim of this study was to investigate the clinical value of hsa-miR-190b-5p in β-thal, and to confirm the regulatory effect of hsa-miR-190b-5p on BCL11A expression. Methods The peripheral blood of 25 pediatric β-thal patients and 25 healthy controls were selected, and qRT-PCR was used to analyze the levels of hsa-miR-190b-5p and BCL11A mRNA. The relationship between hsa-miR-190b-5p expression and hematological parameters was assessed by Pearson’s correlation test. The diagnostic power of hsa-miR-190b-5p was evaluated by ROC curves analysis. The direct integration between hsa-miR-190b-5p and BCL11A 3’-UTR was confirmed by luciferase reporter assay. Results Hsa-miR-190b-5p expression in pediatric β-thal was upregulated, and negatively correlated with the MCH and HbA levels, but positively correlated with the HbF level. Hsa-miR-190b-5p showed a good diagnostic capability for pediatric β-thal equivalent to that of HbA2 (AUC: 0.760 vs. 0.758). Moreover, the levels of BCL11A mRNA in pediatric β-thal were decreased, and hsa-miR-190b-5p had a negative correlation with BCL11A mRNA expression (r = -0.403). BCL11A was a target gene of hsa-miR-190b-5p. The mRNA and protein levels of BCL11A were diminished by introduction of hsa-miR-190b-5p, whereas its expression was upregulated by knockdown of hsa-miR-190b-5p. Conclusions Hsa-miR-190b-5p expression was upregulated in pediatric β-thal and might be an effective diagnostic biomarker. BCL11A was negatively regulated by hsa-miR-190b-5p, which might provide new target for the treatment of pediatric β-thal.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0292031</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>3' Untranslated regions ; Anemia ; Antibodies ; Binding sites ; Biology and Life Sciences ; Biomarkers ; Blood ; Blood diseases ; Chromosome 5 ; Chronic lymphocytic leukemia ; Correlation ; Diagnostic systems ; Epigenetics ; Gene expression ; Hematology ; Hemoglobin ; Lymphoma ; Medicine and Health Sciences ; MicroRNAs ; miRNA ; Pediatrics ; Peripheral blood ; Proteins ; Research and analysis methods ; Software ; Thalassemia ; Transcription factors</subject><ispartof>PloS one, 2023-10, Vol.18 (10), p.e0292031-e0292031</ispartof><rights>2023 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 Chen et al 2023 Chen et al</rights><rights>2023 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Francis</contributor><creatorcontrib>Chen, Meihuan</creatorcontrib><creatorcontrib>Wang, Xinrui</creatorcontrib><creatorcontrib>Wang, Haiwei</creatorcontrib><creatorcontrib>Zhang, Min</creatorcontrib><creatorcontrib>Chen, Lingji</creatorcontrib><creatorcontrib>Chen, Hong</creatorcontrib><creatorcontrib>Pan, Yali</creatorcontrib><creatorcontrib>Zhang, Yanhong</creatorcontrib><creatorcontrib>Xu, Liangpu</creatorcontrib><creatorcontrib>Huang, Hailong</creatorcontrib><title>The clinical value of hsa-miR-190b-5p in peripheral blood of pediatric β-thalassemia and its regulation on BCL11A expression</title><title>PloS one</title><description>Background The B cell CLL/lymphoma 11A (BCL11A) is a key regulator of hemoglobin switching in β-thalassemia (β-thal). Previous study has suggested that dysregulated microRNAs are involved in the regulation of BCL11A expression. The aim of this study was to investigate the clinical value of hsa-miR-190b-5p in β-thal, and to confirm the regulatory effect of hsa-miR-190b-5p on BCL11A expression. Methods The peripheral blood of 25 pediatric β-thal patients and 25 healthy controls were selected, and qRT-PCR was used to analyze the levels of hsa-miR-190b-5p and BCL11A mRNA. The relationship between hsa-miR-190b-5p expression and hematological parameters was assessed by Pearson’s correlation test. The diagnostic power of hsa-miR-190b-5p was evaluated by ROC curves analysis. The direct integration between hsa-miR-190b-5p and BCL11A 3’-UTR was confirmed by luciferase reporter assay. Results Hsa-miR-190b-5p expression in pediatric β-thal was upregulated, and negatively correlated with the MCH and HbA levels, but positively correlated with the HbF level. Hsa-miR-190b-5p showed a good diagnostic capability for pediatric β-thal equivalent to that of HbA2 (AUC: 0.760 vs. 0.758). Moreover, the levels of BCL11A mRNA in pediatric β-thal were decreased, and hsa-miR-190b-5p had a negative correlation with BCL11A mRNA expression (r = -0.403). BCL11A was a target gene of hsa-miR-190b-5p. The mRNA and protein levels of BCL11A were diminished by introduction of hsa-miR-190b-5p, whereas its expression was upregulated by knockdown of hsa-miR-190b-5p. Conclusions Hsa-miR-190b-5p expression was upregulated in pediatric β-thal and might be an effective diagnostic biomarker. BCL11A was negatively regulated by hsa-miR-190b-5p, which might provide new target for the treatment of pediatric β-thal.</description><subject>3' Untranslated regions</subject><subject>Anemia</subject><subject>Antibodies</subject><subject>Binding sites</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Blood</subject><subject>Blood diseases</subject><subject>Chromosome 5</subject><subject>Chronic lymphocytic leukemia</subject><subject>Correlation</subject><subject>Diagnostic systems</subject><subject>Epigenetics</subject><subject>Gene expression</subject><subject>Hematology</subject><subject>Hemoglobin</subject><subject>Lymphoma</subject><subject>Medicine and Health Sciences</subject><subject>MicroRNAs</subject><subject>miRNA</subject><subject>Pediatrics</subject><subject>Peripheral blood</subject><subject>Proteins</subject><subject>Research and analysis methods</subject><subject>Software</subject><subject>Thalassemia</subject><subject>Transcription factors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptkt-K1DAUxosouK6-gWDAG286Jk2atFeyDv5ZGBBkvQ6nyek0Q9rUpF3WC1_KB_GZ7MxUcUUIJPnyyzknJ1-WPWd0w7hirw9hjgP4zRgG3NCiLihnD7ILVvMil8vm4V_rx9mTlA6UlryS8iL7ftMhMd4NzoAnt-BnJKElXYK8d59zVtMmL0fiBjJidGOHccEaH4I9YiNaB1N0hvz8kU8deEgJewcEBkvclEjE_exhcmEgy3i73TF2RfBujJjSIj7NHrXgEz5b58vsy_t3N9uP-e7Th-vt1S43JRVTLmtqitbWBZMgZQ2mMQoU0rKWUNhGKQUVlJSXbJEr0whRMqxVw9pStRYlv8xenOOOPiS9tivpolK8EIJztRDXZ8IGOOgxuh7iNx3A6ZMQ4l5DnJzxqAVtKLbcKmqZAIQKQQoqmloUwhpxzPZmzTY3PVqDw7R07V7Q-yeD6_Q-3GpGy-VbTtW8WiPE8HXGNOneJYPew4BhPhUuCslpWS3oy3_Q_z9PnCkTQ0oR2z_VMKqPHvp9Sx89pFcP8V-1n71-</recordid><startdate>20231005</startdate><enddate>20231005</enddate><creator>Chen, Meihuan</creator><creator>Wang, Xinrui</creator><creator>Wang, Haiwei</creator><creator>Zhang, Min</creator><creator>Chen, Lingji</creator><creator>Chen, Hong</creator><creator>Pan, Yali</creator><creator>Zhang, Yanhong</creator><creator>Xu, Liangpu</creator><creator>Huang, Hailong</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-9675-4039</orcidid><orcidid>https://orcid.org/0000-0001-5775-5082</orcidid></search><sort><creationdate>20231005</creationdate><title>The clinical value of hsa-miR-190b-5p in peripheral blood of pediatric β-thalassemia and its regulation on BCL11A expression</title><author>Chen, Meihuan ; 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Francis</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The clinical value of hsa-miR-190b-5p in peripheral blood of pediatric β-thalassemia and its regulation on BCL11A expression</atitle><jtitle>PloS one</jtitle><date>2023-10-05</date><risdate>2023</risdate><volume>18</volume><issue>10</issue><spage>e0292031</spage><epage>e0292031</epage><pages>e0292031-e0292031</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Background The B cell CLL/lymphoma 11A (BCL11A) is a key regulator of hemoglobin switching in β-thalassemia (β-thal). Previous study has suggested that dysregulated microRNAs are involved in the regulation of BCL11A expression. The aim of this study was to investigate the clinical value of hsa-miR-190b-5p in β-thal, and to confirm the regulatory effect of hsa-miR-190b-5p on BCL11A expression. Methods The peripheral blood of 25 pediatric β-thal patients and 25 healthy controls were selected, and qRT-PCR was used to analyze the levels of hsa-miR-190b-5p and BCL11A mRNA. The relationship between hsa-miR-190b-5p expression and hematological parameters was assessed by Pearson’s correlation test. The diagnostic power of hsa-miR-190b-5p was evaluated by ROC curves analysis. The direct integration between hsa-miR-190b-5p and BCL11A 3’-UTR was confirmed by luciferase reporter assay. Results Hsa-miR-190b-5p expression in pediatric β-thal was upregulated, and negatively correlated with the MCH and HbA levels, but positively correlated with the HbF level. Hsa-miR-190b-5p showed a good diagnostic capability for pediatric β-thal equivalent to that of HbA2 (AUC: 0.760 vs. 0.758). Moreover, the levels of BCL11A mRNA in pediatric β-thal were decreased, and hsa-miR-190b-5p had a negative correlation with BCL11A mRNA expression (r = -0.403). BCL11A was a target gene of hsa-miR-190b-5p. The mRNA and protein levels of BCL11A were diminished by introduction of hsa-miR-190b-5p, whereas its expression was upregulated by knockdown of hsa-miR-190b-5p. Conclusions Hsa-miR-190b-5p expression was upregulated in pediatric β-thal and might be an effective diagnostic biomarker. BCL11A was negatively regulated by hsa-miR-190b-5p, which might provide new target for the treatment of pediatric β-thal.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><doi>10.1371/journal.pone.0292031</doi><orcidid>https://orcid.org/0000-0002-9675-4039</orcidid><orcidid>https://orcid.org/0000-0001-5775-5082</orcidid><oa>free_for_read</oa></addata></record>
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subjects 3' Untranslated regions
Anemia
Antibodies
Binding sites
Biology and Life Sciences
Biomarkers
Blood
Blood diseases
Chromosome 5
Chronic lymphocytic leukemia
Correlation
Diagnostic systems
Epigenetics
Gene expression
Hematology
Hemoglobin
Lymphoma
Medicine and Health Sciences
MicroRNAs
miRNA
Pediatrics
Peripheral blood
Proteins
Research and analysis methods
Software
Thalassemia
Transcription factors
title The clinical value of hsa-miR-190b-5p in peripheral blood of pediatric β-thalassemia and its regulation on BCL11A expression
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