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LINC01137/miR-186-5p/WWOX: a novel axis identified from WWOX-related RNA interactome in bladder cancer

Introduction: The discovery of non-coding RNA (ncRNA) dates back to the pre-genomics era, but the progress in this field is still dynamic and leverages current post-genomics solutions. WWOX is a global gene expression modulator that is scarcely investigated for its role in regulating cancer-related...

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Autores principales: Kołat, Damian, Kałuzińska-Kołat, Żaneta, Kośla, Katarzyna, Orzechowska, Magdalena, Płuciennik, Elżbieta, Bednarek, Andrzej K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10373930/
https://www.ncbi.nlm.nih.gov/pubmed/37519886
http://dx.doi.org/10.3389/fgene.2023.1214968
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author Kołat, Damian
Kałuzińska-Kołat, Żaneta
Kośla, Katarzyna
Orzechowska, Magdalena
Płuciennik, Elżbieta
Bednarek, Andrzej K.
author_facet Kołat, Damian
Kałuzińska-Kołat, Żaneta
Kośla, Katarzyna
Orzechowska, Magdalena
Płuciennik, Elżbieta
Bednarek, Andrzej K.
author_sort Kołat, Damian
collection PubMed
description Introduction: The discovery of non-coding RNA (ncRNA) dates back to the pre-genomics era, but the progress in this field is still dynamic and leverages current post-genomics solutions. WWOX is a global gene expression modulator that is scarcely investigated for its role in regulating cancer-related ncRNAs. In bladder cancer (BLCA), the link between WWOX and ncRNA remains unexplored. The description of AP-2α and AP-2γ transcription factors, known as WWOX-interacting proteins, is more commonplace regarding ncRNA but still merits investigation. Therefore, this in vitro and in silico study aimed to construct an ncRNA-containing network with WWOX/AP-2 and to investigate the most relevant observation in the context of BLCA cell lines and patients. Methods: RT-112, HT-1376, and CAL-29 cell lines were subjected to two stable lentiviral transductions. High-throughput sequencing of cellular variants (deposited in the Gene Expression Omnibus database under the GSE193659 record) enabled the investigation of WWOX/AP-2-dependent differences using various bioinformatics tools (e.g., limma-voom, FactoMineR, multiple Support Vector Machine Recursive Feature Elimination (mSVM-RFE), miRDB, Arena-Idb, ncFANs, RNAhybrid, TargetScan, Protein Annotation Through Evolutionary Relationships (PANTHER), Gene Transcription Regulation Database (GTRD), or Evaluate Cutpoints) and repositories such as The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia. The most relevant observations from cap analysis gene expression sequencing (CAGE-seq) were confirmed using real-time PCR, whereas TCGA data were validated using the GSE31684 cohort. Results: The first stage of the whole study justified focusing solely on WWOX rather than on WWOX combined with AP-2α/γ. The most relevant observation of the developed ncRNA-containing network was LINC01137, i.e., long non-coding RNAs (lncRNAs) that unraveled the core network containing UPF1, ZC3H12A, LINC01137, WWOX, and miR-186-5p, the last three being a novel lncRNA/miRNA/mRNA axis. Patients’ data confirmed the LINC01137/miR-186-5p/WWOX relationship and provided a set of dependent genes (i.e., KRT18, HES1, VCP, FTH1, IFITM3, RAB34, and CLU). Together with the core network, the gene set was subjected to survival analysis for both TCGA-BLCA and GSE31684 patients, which indicated that the increased expression of WWOX or LINC01137 is favorable, similar to their combination with each other (WWOX↑ and LINC01137↑) or with MIR186 (WWOX↑/LINC01137↑ but MIR186↓). Conclusion: WWOX is implicated in the positive feedback loop with LINC01137 that sponges WWOX-targeting miR-186-5p. This novel WWOX-containing lncRNA/miRNA/mRNA axis should be further investigated to depict its relationships in a broader context, which could contribute to BLCA research and treatment.
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spelling pubmed-103739302023-07-28 LINC01137/miR-186-5p/WWOX: a novel axis identified from WWOX-related RNA interactome in bladder cancer Kołat, Damian Kałuzińska-Kołat, Żaneta Kośla, Katarzyna Orzechowska, Magdalena Płuciennik, Elżbieta Bednarek, Andrzej K. Front Genet Genetics Introduction: The discovery of non-coding RNA (ncRNA) dates back to the pre-genomics era, but the progress in this field is still dynamic and leverages current post-genomics solutions. WWOX is a global gene expression modulator that is scarcely investigated for its role in regulating cancer-related ncRNAs. In bladder cancer (BLCA), the link between WWOX and ncRNA remains unexplored. The description of AP-2α and AP-2γ transcription factors, known as WWOX-interacting proteins, is more commonplace regarding ncRNA but still merits investigation. Therefore, this in vitro and in silico study aimed to construct an ncRNA-containing network with WWOX/AP-2 and to investigate the most relevant observation in the context of BLCA cell lines and patients. Methods: RT-112, HT-1376, and CAL-29 cell lines were subjected to two stable lentiviral transductions. High-throughput sequencing of cellular variants (deposited in the Gene Expression Omnibus database under the GSE193659 record) enabled the investigation of WWOX/AP-2-dependent differences using various bioinformatics tools (e.g., limma-voom, FactoMineR, multiple Support Vector Machine Recursive Feature Elimination (mSVM-RFE), miRDB, Arena-Idb, ncFANs, RNAhybrid, TargetScan, Protein Annotation Through Evolutionary Relationships (PANTHER), Gene Transcription Regulation Database (GTRD), or Evaluate Cutpoints) and repositories such as The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia. The most relevant observations from cap analysis gene expression sequencing (CAGE-seq) were confirmed using real-time PCR, whereas TCGA data were validated using the GSE31684 cohort. Results: The first stage of the whole study justified focusing solely on WWOX rather than on WWOX combined with AP-2α/γ. The most relevant observation of the developed ncRNA-containing network was LINC01137, i.e., long non-coding RNAs (lncRNAs) that unraveled the core network containing UPF1, ZC3H12A, LINC01137, WWOX, and miR-186-5p, the last three being a novel lncRNA/miRNA/mRNA axis. Patients’ data confirmed the LINC01137/miR-186-5p/WWOX relationship and provided a set of dependent genes (i.e., KRT18, HES1, VCP, FTH1, IFITM3, RAB34, and CLU). Together with the core network, the gene set was subjected to survival analysis for both TCGA-BLCA and GSE31684 patients, which indicated that the increased expression of WWOX or LINC01137 is favorable, similar to their combination with each other (WWOX↑ and LINC01137↑) or with MIR186 (WWOX↑/LINC01137↑ but MIR186↓). Conclusion: WWOX is implicated in the positive feedback loop with LINC01137 that sponges WWOX-targeting miR-186-5p. This novel WWOX-containing lncRNA/miRNA/mRNA axis should be further investigated to depict its relationships in a broader context, which could contribute to BLCA research and treatment. Frontiers Media S.A. 2023-07-13 /pmc/articles/PMC10373930/ /pubmed/37519886 http://dx.doi.org/10.3389/fgene.2023.1214968 Text en Copyright © 2023 Kołat, Kałuzińska-Kołat, Kośla, Orzechowska, Płuciennik and Bednarek. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Kołat, Damian
Kałuzińska-Kołat, Żaneta
Kośla, Katarzyna
Orzechowska, Magdalena
Płuciennik, Elżbieta
Bednarek, Andrzej K.
LINC01137/miR-186-5p/WWOX: a novel axis identified from WWOX-related RNA interactome in bladder cancer
title LINC01137/miR-186-5p/WWOX: a novel axis identified from WWOX-related RNA interactome in bladder cancer
title_full LINC01137/miR-186-5p/WWOX: a novel axis identified from WWOX-related RNA interactome in bladder cancer
title_fullStr LINC01137/miR-186-5p/WWOX: a novel axis identified from WWOX-related RNA interactome in bladder cancer
title_full_unstemmed LINC01137/miR-186-5p/WWOX: a novel axis identified from WWOX-related RNA interactome in bladder cancer
title_short LINC01137/miR-186-5p/WWOX: a novel axis identified from WWOX-related RNA interactome in bladder cancer
title_sort linc01137/mir-186-5p/wwox: a novel axis identified from wwox-related rna interactome in bladder cancer
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10373930/
https://www.ncbi.nlm.nih.gov/pubmed/37519886
http://dx.doi.org/10.3389/fgene.2023.1214968
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