A Combination of Microarray-Based Profiling and Biocomputational Analysis Identified miR331-3p and hsa-let-7d-5p as Potential Biomarkers of Ulcerative Colitis Progression to Colorectal Cancer
Ulcerative colitis (UC), an inflammatory bowel disease (IBD), may increase the risk of colorectal cancer (CRC) by activating chronic proinflammatory pathways. The goal of this study was to find serum prediction biomarkers in UC to CRC development by combining low-density miRNA microarray and biocomp...
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creator | Chacon-Millan, Pilar Lama, Stefania Del Gaudio, Nunzio Gravina, Antonietta Gerarda Federico, Alessandro Pellegrino, Raffaele Luce, Amalia Altucci, Lucia Facchiano, Angelo Caraglia, Michele Stiuso, Paola |
description | Ulcerative colitis (UC), an inflammatory bowel disease (IBD), may increase the risk of colorectal cancer (CRC) by activating chronic proinflammatory pathways. The goal of this study was to find serum prediction biomarkers in UC to CRC development by combining low-density miRNA microarray and biocomputational approaches. The UC and CRC miRNA expression profiles were compared by low-density miRNA microarray, finding five upregulated miRNAs specific to UC progression to CRC (hsa-let-7d-5p, hsa-miR-16-5p, hsa-miR-145-5p, hsa-miR-223-5p, and hsa-miR-331-3p). The circRNA/miRNA/mRNA competitive endogenous RNA (ceRNA) network analysis showed that the candidate miRNAs were connected to well-known colitis-associated CRC ACVR2A, SOCS1, IGF2BP1, FAM126A, and CCDC85C mRNAs, and circ-SHPRH circRNA. SST and SCARA5 genes regulated by hsa-let-7d-5p, hsa-miR-145-5p, and hsa-miR-331-3p were linked to a poor survival prognosis in a CRC patient dataset from The Cancer Genome Atlas (TCGA). Lastly, our mRNA and miRNA candidates were validated by comparing their expression to differentially expressed mRNAs and miRNAs from colitis-associated CRC tissue databases. A high level of hsa-miR-331-3p and a parallel reduction in SOCS1 mRNA were found in tissue and serum. We propose hsa-miR-331-3p and possibly hsa-let-7d-5p as novel serum biomarkers for predicting UC progression to CRC. More clinical sample analysis is required for further validation. |
doi_str_mv | 10.3390/ijms25115699 |
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The goal of this study was to find serum prediction biomarkers in UC to CRC development by combining low-density miRNA microarray and biocomputational approaches. The UC and CRC miRNA expression profiles were compared by low-density miRNA microarray, finding five upregulated miRNAs specific to UC progression to CRC (hsa-let-7d-5p, hsa-miR-16-5p, hsa-miR-145-5p, hsa-miR-223-5p, and hsa-miR-331-3p). The circRNA/miRNA/mRNA competitive endogenous RNA (ceRNA) network analysis showed that the candidate miRNAs were connected to well-known colitis-associated CRC ACVR2A, SOCS1, IGF2BP1, FAM126A, and CCDC85C mRNAs, and circ-SHPRH circRNA. SST and SCARA5 genes regulated by hsa-let-7d-5p, hsa-miR-145-5p, and hsa-miR-331-3p were linked to a poor survival prognosis in a CRC patient dataset from The Cancer Genome Atlas (TCGA). Lastly, our mRNA and miRNA candidates were validated by comparing their expression to differentially expressed mRNAs and miRNAs from colitis-associated CRC tissue databases. A high level of hsa-miR-331-3p and a parallel reduction in SOCS1 mRNA were found in tissue and serum. We propose hsa-miR-331-3p and possibly hsa-let-7d-5p as novel serum biomarkers for predicting UC progression to CRC. More clinical sample analysis is required for further validation.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms25115699</identifier><identifier>PMID: 38891888</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adult ; Apoptosis ; Biological markers ; Biomarkers ; Biomarkers, Tumor - genetics ; Cancer ; Cell cycle ; Colitis, Ulcerative - genetics ; Colitis, Ulcerative - pathology ; Colorectal cancer ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - pathology ; Comparative analysis ; Computational Biology - methods ; Development and progression ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Genes ; Health aspects ; Health savings accounts ; Humans ; Inflammation ; Inflammatory bowel disease ; Male ; Medical prognosis ; Microbiota ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; Middle Aged ; Oncology, Experimental ; Pathogenesis ; Patients ; Proteins ; Scientific equipment and supplies industry ; Ulcerative colitis</subject><ispartof>International journal of molecular sciences, 2024-06, Vol.25 (11), p.5699</ispartof><rights>COPYRIGHT 2024 MDPI AG</rights><rights>2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 by the authors. 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c367t-3ed88124db26c15d1dc1037ce1f55ffce97bb0fd2b0f79e32b4e961c2ad54ce33</cites><orcidid>0000-0002-7312-5387 ; 0000-0001-5074-230X ; 0000-0002-9972-1291 ; 0000-0001-8049-0115 ; 0000-0003-0372-6870 ; 0000-0003-2408-6091 ; 0000-0002-0885-0793 ; 0000-0001-5096-7488</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11171846/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11171846/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38891888$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chacon-Millan, Pilar</creatorcontrib><creatorcontrib>Lama, Stefania</creatorcontrib><creatorcontrib>Del Gaudio, Nunzio</creatorcontrib><creatorcontrib>Gravina, Antonietta Gerarda</creatorcontrib><creatorcontrib>Federico, Alessandro</creatorcontrib><creatorcontrib>Pellegrino, Raffaele</creatorcontrib><creatorcontrib>Luce, Amalia</creatorcontrib><creatorcontrib>Altucci, Lucia</creatorcontrib><creatorcontrib>Facchiano, Angelo</creatorcontrib><creatorcontrib>Caraglia, Michele</creatorcontrib><creatorcontrib>Stiuso, Paola</creatorcontrib><title>A Combination of Microarray-Based Profiling and Biocomputational Analysis Identified miR331-3p and hsa-let-7d-5p as Potential Biomarkers of Ulcerative Colitis Progression to Colorectal Cancer</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Ulcerative colitis (UC), an inflammatory bowel disease (IBD), may increase the risk of colorectal cancer (CRC) by activating chronic proinflammatory pathways. The goal of this study was to find serum prediction biomarkers in UC to CRC development by combining low-density miRNA microarray and biocomputational approaches. The UC and CRC miRNA expression profiles were compared by low-density miRNA microarray, finding five upregulated miRNAs specific to UC progression to CRC (hsa-let-7d-5p, hsa-miR-16-5p, hsa-miR-145-5p, hsa-miR-223-5p, and hsa-miR-331-3p). The circRNA/miRNA/mRNA competitive endogenous RNA (ceRNA) network analysis showed that the candidate miRNAs were connected to well-known colitis-associated CRC ACVR2A, SOCS1, IGF2BP1, FAM126A, and CCDC85C mRNAs, and circ-SHPRH circRNA. SST and SCARA5 genes regulated by hsa-let-7d-5p, hsa-miR-145-5p, and hsa-miR-331-3p were linked to a poor survival prognosis in a CRC patient dataset from The Cancer Genome Atlas (TCGA). Lastly, our mRNA and miRNA candidates were validated by comparing their expression to differentially expressed mRNAs and miRNAs from colitis-associated CRC tissue databases. A high level of hsa-miR-331-3p and a parallel reduction in SOCS1 mRNA were found in tissue and serum. We propose hsa-miR-331-3p and possibly hsa-let-7d-5p as novel serum biomarkers for predicting UC progression to CRC. More clinical sample analysis is required for further validation.</description><subject>Adult</subject><subject>Apoptosis</subject><subject>Biological markers</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Cancer</subject><subject>Cell cycle</subject><subject>Colitis, Ulcerative - genetics</subject><subject>Colitis, Ulcerative - pathology</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Comparative analysis</subject><subject>Computational Biology - methods</subject><subject>Development and progression</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Regulatory Networks</subject><subject>Genes</subject><subject>Health aspects</subject><subject>Health savings accounts</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammatory bowel disease</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Microbiota</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>Middle Aged</subject><subject>Oncology, Experimental</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>Proteins</subject><subject>Scientific equipment and supplies industry</subject><subject>Ulcerative colitis</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptkk1v1DAQhiMEoh9w44wiceHQFH8ksX1C2xUflYqoED1bjj3eeknixc5W2l_HX2PSlrJFyNLYsp_3nbE9RfGKklPOFXkX1kNmDaVNq9ST4pDWjFWEtOLp3vqgOMp5TQjjrFHPiwMupaJSysPi16JcxqELo5lCHMvoyy_BpmhSMrvqzGRw5WWKPvRhXJVmdOVZiDYOm-10KzB9ucCwyyGX5w7GKfiAkiF845xWfHMruc6m6mGqhKsa3MnlZZxmFMXoNpj0A1KeU1_1FhL63gAW1YcJTTH5KkHOc3FTnLdjAjuhdGlGpF8Uz7zpM7y8n4-Lq48fvi8_VxdfP50vFxeV5a2YKg5OSspq17HW0sZRZynhwgL1TeO9BSW6jnjHMAgFnHU1qJZaZlxTW-D8uHh_57vZdgM4i_Un0-tNClj_TkcT9OOTMVzrVbzRlFJBZd2iw9t7hxR_biFPegjZQt-bEeI2a04EEUqxmiH65h90HbcJ33mmWlFLxoj4S61MDzqMPmJiO5vqhVBCKknUTJ3-h8LhYAg2joB_C48FJ3cCbIOcE_iHS1Ki547T-x2H-Ov9h3mA_7QY_w1b6tRf</recordid><startdate>20240601</startdate><enddate>20240601</enddate><creator>Chacon-Millan, Pilar</creator><creator>Lama, Stefania</creator><creator>Del Gaudio, Nunzio</creator><creator>Gravina, Antonietta Gerarda</creator><creator>Federico, Alessandro</creator><creator>Pellegrino, Raffaele</creator><creator>Luce, Amalia</creator><creator>Altucci, Lucia</creator><creator>Facchiano, Angelo</creator><creator>Caraglia, Michele</creator><creator>Stiuso, Paola</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7312-5387</orcidid><orcidid>https://orcid.org/0000-0001-5074-230X</orcidid><orcidid>https://orcid.org/0000-0002-9972-1291</orcidid><orcidid>https://orcid.org/0000-0001-8049-0115</orcidid><orcidid>https://orcid.org/0000-0003-0372-6870</orcidid><orcidid>https://orcid.org/0000-0003-2408-6091</orcidid><orcidid>https://orcid.org/0000-0002-0885-0793</orcidid><orcidid>https://orcid.org/0000-0001-5096-7488</orcidid></search><sort><creationdate>20240601</creationdate><title>A Combination of Microarray-Based Profiling and Biocomputational Analysis Identified miR331-3p and hsa-let-7d-5p as Potential Biomarkers of Ulcerative Colitis Progression to Colorectal Cancer</title><author>Chacon-Millan, Pilar ; Lama, Stefania ; Del Gaudio, Nunzio ; Gravina, Antonietta Gerarda ; Federico, Alessandro ; Pellegrino, Raffaele ; Luce, Amalia ; Altucci, Lucia ; Facchiano, Angelo ; Caraglia, Michele ; Stiuso, Paola</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c367t-3ed88124db26c15d1dc1037ce1f55ffce97bb0fd2b0f79e32b4e961c2ad54ce33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Apoptosis</topic><topic>Biological markers</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Cancer</topic><topic>Cell cycle</topic><topic>Colitis, Ulcerative - genetics</topic><topic>Colitis, Ulcerative - pathology</topic><topic>Colorectal cancer</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Comparative analysis</topic><topic>Computational Biology - methods</topic><topic>Development and progression</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Regulatory Networks</topic><topic>Genes</topic><topic>Health aspects</topic><topic>Health savings accounts</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Inflammatory bowel disease</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Microbiota</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>Middle Aged</topic><topic>Oncology, Experimental</topic><topic>Pathogenesis</topic><topic>Patients</topic><topic>Proteins</topic><topic>Scientific equipment and supplies industry</topic><topic>Ulcerative colitis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chacon-Millan, Pilar</creatorcontrib><creatorcontrib>Lama, Stefania</creatorcontrib><creatorcontrib>Del Gaudio, Nunzio</creatorcontrib><creatorcontrib>Gravina, Antonietta Gerarda</creatorcontrib><creatorcontrib>Federico, Alessandro</creatorcontrib><creatorcontrib>Pellegrino, Raffaele</creatorcontrib><creatorcontrib>Luce, Amalia</creatorcontrib><creatorcontrib>Altucci, Lucia</creatorcontrib><creatorcontrib>Facchiano, Angelo</creatorcontrib><creatorcontrib>Caraglia, Michele</creatorcontrib><creatorcontrib>Stiuso, Paola</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - 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The goal of this study was to find serum prediction biomarkers in UC to CRC development by combining low-density miRNA microarray and biocomputational approaches. The UC and CRC miRNA expression profiles were compared by low-density miRNA microarray, finding five upregulated miRNAs specific to UC progression to CRC (hsa-let-7d-5p, hsa-miR-16-5p, hsa-miR-145-5p, hsa-miR-223-5p, and hsa-miR-331-3p). The circRNA/miRNA/mRNA competitive endogenous RNA (ceRNA) network analysis showed that the candidate miRNAs were connected to well-known colitis-associated CRC ACVR2A, SOCS1, IGF2BP1, FAM126A, and CCDC85C mRNAs, and circ-SHPRH circRNA. SST and SCARA5 genes regulated by hsa-let-7d-5p, hsa-miR-145-5p, and hsa-miR-331-3p were linked to a poor survival prognosis in a CRC patient dataset from The Cancer Genome Atlas (TCGA). Lastly, our mRNA and miRNA candidates were validated by comparing their expression to differentially expressed mRNAs and miRNAs from colitis-associated CRC tissue databases. A high level of hsa-miR-331-3p and a parallel reduction in SOCS1 mRNA were found in tissue and serum. We propose hsa-miR-331-3p and possibly hsa-let-7d-5p as novel serum biomarkers for predicting UC progression to CRC. More clinical sample analysis is required for further validation.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>38891888</pmid><doi>10.3390/ijms25115699</doi><orcidid>https://orcid.org/0000-0002-7312-5387</orcidid><orcidid>https://orcid.org/0000-0001-5074-230X</orcidid><orcidid>https://orcid.org/0000-0002-9972-1291</orcidid><orcidid>https://orcid.org/0000-0001-8049-0115</orcidid><orcidid>https://orcid.org/0000-0003-0372-6870</orcidid><orcidid>https://orcid.org/0000-0003-2408-6091</orcidid><orcidid>https://orcid.org/0000-0002-0885-0793</orcidid><orcidid>https://orcid.org/0000-0001-5096-7488</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adult Apoptosis Biological markers Biomarkers Biomarkers, Tumor - genetics Cancer Cell cycle Colitis, Ulcerative - genetics Colitis, Ulcerative - pathology Colorectal cancer Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology Comparative analysis Computational Biology - methods Development and progression Disease Progression Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Gene Regulatory Networks Genes Health aspects Health savings accounts Humans Inflammation Inflammatory bowel disease Male Medical prognosis Microbiota MicroRNA MicroRNAs MicroRNAs - genetics Middle Aged Oncology, Experimental Pathogenesis Patients Proteins Scientific equipment and supplies industry Ulcerative colitis |
title | A Combination of Microarray-Based Profiling and Biocomputational Analysis Identified miR331-3p and hsa-let-7d-5p as Potential Biomarkers of Ulcerative Colitis Progression to Colorectal Cancer |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T10%3A37%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20Combination%20of%20Microarray-Based%20Profiling%20and%20Biocomputational%20Analysis%20Identified%20miR331-3p%20and%20hsa-let-7d-5p%20as%20Potential%20Biomarkers%20of%20Ulcerative%20Colitis%20Progression%20to%20Colorectal%20Cancer&rft.jtitle=International%20journal%20of%20molecular%20sciences&rft.au=Chacon-Millan,%20Pilar&rft.date=2024-06-01&rft.volume=25&rft.issue=11&rft.spage=5699&rft.pages=5699-&rft.issn=1422-0067&rft.eissn=1422-0067&rft_id=info:doi/10.3390/ijms25115699&rft_dat=%3Cgale_pubme%3EA797898097%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3067482207&rft_id=info:pmid/38891888&rft_galeid=A797898097&rfr_iscdi=true |