Loading…

Integrated Network Analysis of microRNAs, mRNAs, and Proteins Reveals the Regulatory Interaction between hsa-mir-200b and CFL2 Associated with Advanced Stage and Poor Prognosis in Patients with Intestinal Gastric Cancer

Intestinal gastric cancer (IGC) carcinogenesis results from a complex interplay between environmental and molecular factors, ultimately contributing to disease development. We used integrative bioinformatic analysis to investigate IGC high-throughput molecular data to uncover interactions among diff...

Full description

Saved in:
Bibliographic Details
Published in:Cancers 2023-11, Vol.15 (22), p.5374
Main Authors: dos Santos, Everton Cruz, Rohan, Paulo, Binato, Renata, Abdelhay, Eliana
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c410t-c7fa29dcb8d77e548065a54b9b0eb3494aa598d9892f66a9bb66740d211ba3393
cites cdi_FETCH-LOGICAL-c410t-c7fa29dcb8d77e548065a54b9b0eb3494aa598d9892f66a9bb66740d211ba3393
container_end_page
container_issue 22
container_start_page 5374
container_title Cancers
container_volume 15
creator dos Santos, Everton Cruz
Rohan, Paulo
Binato, Renata
Abdelhay, Eliana
description Intestinal gastric cancer (IGC) carcinogenesis results from a complex interplay between environmental and molecular factors, ultimately contributing to disease development. We used integrative bioinformatic analysis to investigate IGC high-throughput molecular data to uncover interactions among differentially expressed genes, microRNAs, and proteins and their roles in IGC. An integrated network was generated based on experimentally validated microRNA-gene/protein interaction data, with three regulatory circuits involved in a complex network contributing to IGC progression. Key regulators were determined, including 23 microRNA and 15 gene/protein hubs. The regulatory circuit networks were associated with hallmarks of cancer, e.g., cell death, apoptosis and the cell cycle, the immune response, and epithelial-to-mesenchymal transition, indicating that different mechanisms of gene regulation impact similar biological functions. Altered expression of hubs was related to the clinicopathological characteristics of IGC patients and showed good performance in discriminating tumors from adjacent nontumor tissues and in relation to T stage and overall survival (OS). Interestingly, expression of upregulated hub hsa-mir-200b and its downregulated target hub gene/protein CFL2 were related not only to pathological T staging and OS but also to changes during IGC carcinogenesis. Our study suggests that regulation of CFL2 by hsa-miR-200b is a dynamic process during tumor progression and that this control plays essential roles in IGC development. Overall, the results indicate that this regulatory interaction is an important component in IGC pathogenesis. Also, we identified a novel molecular interplay between microRNAs, proteins, and genes associated with IGC in a complex biological network and the hubs closely related to IGC carcinogenesis as potential biomarkers.
doi_str_mv 10.3390/cancers15225374
format article
fullrecord <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_2893845281</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A774318345</galeid><sourcerecordid>A774318345</sourcerecordid><originalsourceid>FETCH-LOGICAL-c410t-c7fa29dcb8d77e548065a54b9b0eb3494aa598d9892f66a9bb66740d211ba3393</originalsourceid><addsrcrecordid>eNptUsFu1DAQjRBIVKVnrpa4cCCtYztxfIxWtFRalarAOZo4k6xLYhfb22q_lZ_B2XAoFfZhRtab955nJsveF_Scc0UvNFiNPhQlYyWX4lV2wqhkeVUp8fpZ_jY7C-GepsN5ISt5kv2-thFHDxF7coPxyfmfpLEwHYIJxA1kNtq7u5smfCLzGsD25Na7iMYGcoePCFMgcYcpH_cTROcPZCH1oKNxlnSJFdGSXYB8Nj5nlHZHks3llpEmBKfNUf7JxB1p-sflKz35FmHEVcw5vyiO1i2mjCW3EA3aGNaSRSxEk0yTKwjRG002x3a8y94MyRye_Y2n2Y_Lz983X_Lt16vrTbPNtShozLUcgKled3UvJZaiplUJpehUR7HjQgmAUtW9qhUbqgpU11WVFLRnRdFB6j4_zT6uvA_e_donL-1sgsZpAotuH1pWK16LktVFgn54Ab13e5-sryjKZV08Q40wYWvs4GLq5kLaNlIKXtRclAl1_h9Uuj2mqTmLg0nv_xRcrAVppCF4HNoHb2bwh7ag7bJG7Ys14n8A91G8tQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2893037811</pqid></control><display><type>article</type><title>Integrated Network Analysis of microRNAs, mRNAs, and Proteins Reveals the Regulatory Interaction between hsa-mir-200b and CFL2 Associated with Advanced Stage and Poor Prognosis in Patients with Intestinal Gastric Cancer</title><source>PubMed (Medline)</source><source>Publicly Available Content Database</source><creator>dos Santos, Everton Cruz ; Rohan, Paulo ; Binato, Renata ; Abdelhay, Eliana</creator><creatorcontrib>dos Santos, Everton Cruz ; Rohan, Paulo ; Binato, Renata ; Abdelhay, Eliana</creatorcontrib><description>Intestinal gastric cancer (IGC) carcinogenesis results from a complex interplay between environmental and molecular factors, ultimately contributing to disease development. We used integrative bioinformatic analysis to investigate IGC high-throughput molecular data to uncover interactions among differentially expressed genes, microRNAs, and proteins and their roles in IGC. An integrated network was generated based on experimentally validated microRNA-gene/protein interaction data, with three regulatory circuits involved in a complex network contributing to IGC progression. Key regulators were determined, including 23 microRNA and 15 gene/protein hubs. The regulatory circuit networks were associated with hallmarks of cancer, e.g., cell death, apoptosis and the cell cycle, the immune response, and epithelial-to-mesenchymal transition, indicating that different mechanisms of gene regulation impact similar biological functions. Altered expression of hubs was related to the clinicopathological characteristics of IGC patients and showed good performance in discriminating tumors from adjacent nontumor tissues and in relation to T stage and overall survival (OS). Interestingly, expression of upregulated hub hsa-mir-200b and its downregulated target hub gene/protein CFL2 were related not only to pathological T staging and OS but also to changes during IGC carcinogenesis. Our study suggests that regulation of CFL2 by hsa-miR-200b is a dynamic process during tumor progression and that this control plays essential roles in IGC development. Overall, the results indicate that this regulatory interaction is an important component in IGC pathogenesis. Also, we identified a novel molecular interplay between microRNAs, proteins, and genes associated with IGC in a complex biological network and the hubs closely related to IGC carcinogenesis as potential biomarkers.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers15225374</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Apoptosis ; Biomarkers ; Cancer ; Cancer patients ; Carcinogenesis ; Cell cycle ; Cell death ; Development and progression ; Gastric cancer ; Gene expression ; Gene regulation ; Genes ; Genomes ; Health savings accounts ; Immune response ; Intestine ; Medical prognosis ; Messenger RNA ; MicroRNA ; MicroRNAs ; miRNA ; mRNA ; Patients ; Performance evaluation ; Proteins ; Software ; Stem cells ; Stomach cancer ; Survival analysis ; Tumors</subject><ispartof>Cancers, 2023-11, Vol.15 (22), p.5374</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 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><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c410t-c7fa29dcb8d77e548065a54b9b0eb3494aa598d9892f66a9bb66740d211ba3393</citedby><cites>FETCH-LOGICAL-c410t-c7fa29dcb8d77e548065a54b9b0eb3494aa598d9892f66a9bb66740d211ba3393</cites><orcidid>0000-0002-3412-5325 ; 0000-0001-5166-0832</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2893037811/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2893037811?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,25753,27924,27925,37012,37013,44590,75126</link.rule.ids></links><search><creatorcontrib>dos Santos, Everton Cruz</creatorcontrib><creatorcontrib>Rohan, Paulo</creatorcontrib><creatorcontrib>Binato, Renata</creatorcontrib><creatorcontrib>Abdelhay, Eliana</creatorcontrib><title>Integrated Network Analysis of microRNAs, mRNAs, and Proteins Reveals the Regulatory Interaction between hsa-mir-200b and CFL2 Associated with Advanced Stage and Poor Prognosis in Patients with Intestinal Gastric Cancer</title><title>Cancers</title><description>Intestinal gastric cancer (IGC) carcinogenesis results from a complex interplay between environmental and molecular factors, ultimately contributing to disease development. We used integrative bioinformatic analysis to investigate IGC high-throughput molecular data to uncover interactions among differentially expressed genes, microRNAs, and proteins and their roles in IGC. An integrated network was generated based on experimentally validated microRNA-gene/protein interaction data, with three regulatory circuits involved in a complex network contributing to IGC progression. Key regulators were determined, including 23 microRNA and 15 gene/protein hubs. The regulatory circuit networks were associated with hallmarks of cancer, e.g., cell death, apoptosis and the cell cycle, the immune response, and epithelial-to-mesenchymal transition, indicating that different mechanisms of gene regulation impact similar biological functions. Altered expression of hubs was related to the clinicopathological characteristics of IGC patients and showed good performance in discriminating tumors from adjacent nontumor tissues and in relation to T stage and overall survival (OS). Interestingly, expression of upregulated hub hsa-mir-200b and its downregulated target hub gene/protein CFL2 were related not only to pathological T staging and OS but also to changes during IGC carcinogenesis. Our study suggests that regulation of CFL2 by hsa-miR-200b is a dynamic process during tumor progression and that this control plays essential roles in IGC development. Overall, the results indicate that this regulatory interaction is an important component in IGC pathogenesis. Also, we identified a novel molecular interplay between microRNAs, proteins, and genes associated with IGC in a complex biological network and the hubs closely related to IGC carcinogenesis as potential biomarkers.</description><subject>Apoptosis</subject><subject>Biomarkers</subject><subject>Cancer</subject><subject>Cancer patients</subject><subject>Carcinogenesis</subject><subject>Cell cycle</subject><subject>Cell death</subject><subject>Development and progression</subject><subject>Gastric cancer</subject><subject>Gene expression</subject><subject>Gene regulation</subject><subject>Genes</subject><subject>Genomes</subject><subject>Health savings accounts</subject><subject>Immune response</subject><subject>Intestine</subject><subject>Medical prognosis</subject><subject>Messenger RNA</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>miRNA</subject><subject>mRNA</subject><subject>Patients</subject><subject>Performance evaluation</subject><subject>Proteins</subject><subject>Software</subject><subject>Stem cells</subject><subject>Stomach cancer</subject><subject>Survival analysis</subject><subject>Tumors</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNptUsFu1DAQjRBIVKVnrpa4cCCtYztxfIxWtFRalarAOZo4k6xLYhfb22q_lZ_B2XAoFfZhRtab955nJsveF_Scc0UvNFiNPhQlYyWX4lV2wqhkeVUp8fpZ_jY7C-GepsN5ISt5kv2-thFHDxF7coPxyfmfpLEwHYIJxA1kNtq7u5smfCLzGsD25Na7iMYGcoePCFMgcYcpH_cTROcPZCH1oKNxlnSJFdGSXYB8Nj5nlHZHks3llpEmBKfNUf7JxB1p-sflKz35FmHEVcw5vyiO1i2mjCW3EA3aGNaSRSxEk0yTKwjRG002x3a8y94MyRye_Y2n2Y_Lz983X_Lt16vrTbPNtShozLUcgKled3UvJZaiplUJpehUR7HjQgmAUtW9qhUbqgpU11WVFLRnRdFB6j4_zT6uvA_e_donL-1sgsZpAotuH1pWK16LktVFgn54Ab13e5-sryjKZV08Q40wYWvs4GLq5kLaNlIKXtRclAl1_h9Uuj2mqTmLg0nv_xRcrAVppCF4HNoHb2bwh7ag7bJG7Ys14n8A91G8tQ</recordid><startdate>20231101</startdate><enddate>20231101</enddate><creator>dos Santos, Everton Cruz</creator><creator>Rohan, Paulo</creator><creator>Binato, Renata</creator><creator>Abdelhay, Eliana</creator><general>MDPI AG</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</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><orcidid>https://orcid.org/0000-0002-3412-5325</orcidid><orcidid>https://orcid.org/0000-0001-5166-0832</orcidid></search><sort><creationdate>20231101</creationdate><title>Integrated Network Analysis of microRNAs, mRNAs, and Proteins Reveals the Regulatory Interaction between hsa-mir-200b and CFL2 Associated with Advanced Stage and Poor Prognosis in Patients with Intestinal Gastric Cancer</title><author>dos Santos, Everton Cruz ; Rohan, Paulo ; Binato, Renata ; Abdelhay, Eliana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c410t-c7fa29dcb8d77e548065a54b9b0eb3494aa598d9892f66a9bb66740d211ba3393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Apoptosis</topic><topic>Biomarkers</topic><topic>Cancer</topic><topic>Cancer patients</topic><topic>Carcinogenesis</topic><topic>Cell cycle</topic><topic>Cell death</topic><topic>Development and progression</topic><topic>Gastric cancer</topic><topic>Gene expression</topic><topic>Gene regulation</topic><topic>Genes</topic><topic>Genomes</topic><topic>Health savings accounts</topic><topic>Immune response</topic><topic>Intestine</topic><topic>Medical prognosis</topic><topic>Messenger RNA</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>miRNA</topic><topic>mRNA</topic><topic>Patients</topic><topic>Performance evaluation</topic><topic>Proteins</topic><topic>Software</topic><topic>Stem cells</topic><topic>Stomach cancer</topic><topic>Survival analysis</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>dos Santos, Everton Cruz</creatorcontrib><creatorcontrib>Rohan, Paulo</creatorcontrib><creatorcontrib>Binato, Renata</creatorcontrib><creatorcontrib>Abdelhay, Eliana</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>ProQuest research library</collection><collection>Biological Science Database</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 - Academic</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>dos Santos, Everton Cruz</au><au>Rohan, Paulo</au><au>Binato, Renata</au><au>Abdelhay, Eliana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Integrated Network Analysis of microRNAs, mRNAs, and Proteins Reveals the Regulatory Interaction between hsa-mir-200b and CFL2 Associated with Advanced Stage and Poor Prognosis in Patients with Intestinal Gastric Cancer</atitle><jtitle>Cancers</jtitle><date>2023-11-01</date><risdate>2023</risdate><volume>15</volume><issue>22</issue><spage>5374</spage><pages>5374-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Intestinal gastric cancer (IGC) carcinogenesis results from a complex interplay between environmental and molecular factors, ultimately contributing to disease development. We used integrative bioinformatic analysis to investigate IGC high-throughput molecular data to uncover interactions among differentially expressed genes, microRNAs, and proteins and their roles in IGC. An integrated network was generated based on experimentally validated microRNA-gene/protein interaction data, with three regulatory circuits involved in a complex network contributing to IGC progression. Key regulators were determined, including 23 microRNA and 15 gene/protein hubs. The regulatory circuit networks were associated with hallmarks of cancer, e.g., cell death, apoptosis and the cell cycle, the immune response, and epithelial-to-mesenchymal transition, indicating that different mechanisms of gene regulation impact similar biological functions. Altered expression of hubs was related to the clinicopathological characteristics of IGC patients and showed good performance in discriminating tumors from adjacent nontumor tissues and in relation to T stage and overall survival (OS). Interestingly, expression of upregulated hub hsa-mir-200b and its downregulated target hub gene/protein CFL2 were related not only to pathological T staging and OS but also to changes during IGC carcinogenesis. Our study suggests that regulation of CFL2 by hsa-miR-200b is a dynamic process during tumor progression and that this control plays essential roles in IGC development. Overall, the results indicate that this regulatory interaction is an important component in IGC pathogenesis. Also, we identified a novel molecular interplay between microRNAs, proteins, and genes associated with IGC in a complex biological network and the hubs closely related to IGC carcinogenesis as potential biomarkers.</abstract><cop>Basel</cop><pub>MDPI AG</pub><doi>10.3390/cancers15225374</doi><orcidid>https://orcid.org/0000-0002-3412-5325</orcidid><orcidid>https://orcid.org/0000-0001-5166-0832</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2072-6694
ispartof Cancers, 2023-11, Vol.15 (22), p.5374
issn 2072-6694
2072-6694
language eng
recordid cdi_proquest_miscellaneous_2893845281
source PubMed (Medline); Publicly Available Content Database
subjects Apoptosis
Biomarkers
Cancer
Cancer patients
Carcinogenesis
Cell cycle
Cell death
Development and progression
Gastric cancer
Gene expression
Gene regulation
Genes
Genomes
Health savings accounts
Immune response
Intestine
Medical prognosis
Messenger RNA
MicroRNA
MicroRNAs
miRNA
mRNA
Patients
Performance evaluation
Proteins
Software
Stem cells
Stomach cancer
Survival analysis
Tumors
title Integrated Network Analysis of microRNAs, mRNAs, and Proteins Reveals the Regulatory Interaction between hsa-mir-200b and CFL2 Associated with Advanced Stage and Poor Prognosis in Patients with Intestinal Gastric Cancer
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T13%3A25%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Integrated%20Network%20Analysis%20of%20microRNAs,%20mRNAs,%20and%20Proteins%20Reveals%20the%20Regulatory%20Interaction%20between%20hsa-mir-200b%20and%20CFL2%20Associated%20with%20Advanced%20Stage%20and%20Poor%20Prognosis%20in%20Patients%20with%20Intestinal%20Gastric%20Cancer&rft.jtitle=Cancers&rft.au=dos%20Santos,%20Everton%20Cruz&rft.date=2023-11-01&rft.volume=15&rft.issue=22&rft.spage=5374&rft.pages=5374-&rft.issn=2072-6694&rft.eissn=2072-6694&rft_id=info:doi/10.3390/cancers15225374&rft_dat=%3Cgale_proqu%3EA774318345%3C/gale_proqu%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c410t-c7fa29dcb8d77e548065a54b9b0eb3494aa598d9892f66a9bb66740d211ba3393%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2893037811&rft_id=info:pmid/&rft_galeid=A774318345&rfr_iscdi=true