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Long Non-Coding RNAs Associated with Mitogen-Activated Protein Kinase in Human Pancreatic Cancer

SIMPLE SUMMARY: Long non-coding RNAs (lncRNAs) have emerged as a significant player in various cancers, including pancreatic cancer. However, how lncRNAs are aberrantly expressed in cancers is largely unknown. We hypothesized that lncRNAs would be regulated by signaling pathways and contribute to ma...

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Autores principales: Ishikawa, Tomohiko, Fukushige, Shinichi, Saiki, Yuriko, Hirose, Katsuya, Hiyoshi, Takako, Ogawa, Takenori, Katori, Yukio, Furukawa, Toru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818929/
https://www.ncbi.nlm.nih.gov/pubmed/36612299
http://dx.doi.org/10.3390/cancers15010303
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author Ishikawa, Tomohiko
Fukushige, Shinichi
Saiki, Yuriko
Hirose, Katsuya
Hiyoshi, Takako
Ogawa, Takenori
Katori, Yukio
Furukawa, Toru
author_facet Ishikawa, Tomohiko
Fukushige, Shinichi
Saiki, Yuriko
Hirose, Katsuya
Hiyoshi, Takako
Ogawa, Takenori
Katori, Yukio
Furukawa, Toru
author_sort Ishikawa, Tomohiko
collection PubMed
description SIMPLE SUMMARY: Long non-coding RNAs (lncRNAs) have emerged as a significant player in various cancers, including pancreatic cancer. However, how lncRNAs are aberrantly expressed in cancers is largely unknown. We hypothesized that lncRNAs would be regulated by signaling pathways and contribute to malignant phenotypes of cancer. In this study, to understand the significance of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) for the expression of lncRNAs in pancreatic cancer, we performed comparative transcriptome analyses between pancreatic cancer cell lines with or without activation of MAPK. We identified 45 lncRNAs presumably associated with MAPK in pancreatic cancer cells; among these, LINC00941 was consistently upregulated by MAPK. The promoter of LINC00941 was determined and found to be preferentially associated with MAPK activity via ETS-1 binding site. TCGA data analysis indicated that high expression of LINC00941 was associated with poor prognosis of pancreatic cancer patients. Downstream targets of LINC00941 were involved in 44 biological processes, including the glycoprotein biosynthetic process, beta-catenin-TCF complex assembly, and histone modification. These results indicate that MAPK mediates the aberrant expression of lncRNAs, and LINC00941 is the most consistently promoted lncRNA by MAPK in pancreatic cancer. Therefore, MAPK-associated lncRNAs might represent both potentially valid therapeutic targets and diagnostic biomarkers. ABSTRACT: Long non-coding RNAs (lncRNAs) have emerged as a significant player in various cancers, including pancreatic cancer. However, how lncRNAs are aberrantly expressed in cancers is largely unknown. We hypothesized that lncRNAs would be regulated by signaling pathways and contribute to malignant phenotypes of cancer. In this study, to understand the significance of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), which is a major aberrant signaling pathway in pancreatic cancer, for the expression of lncRNAs, we performed comparative transcriptome analyses between pancreatic cancer cell lines with or without activation of MAPK. We identified 45 lncRNAs presumably associated with MAPK in pancreatic cancer cells; among these, LINC00941 was consistently upregulated by MAPK. The immediate genomic upstream region flanking LINC00941 was identified as a promoter region, the activity of which was found to be preferentially associated with MAPK activity via ETS-1 binding site. LINC00941 promoted cell proliferation in vitro. Moreover, TCGA data analysis indicated that high expression of LINC00941 was associated with poor prognosis of patients with pancreatic cancer. Transcriptomes comparing transcriptions between cells with and without LINC00941 knockdown revealed 3229 differentially expressed genes involved in 44 biological processes, including the glycoprotein biosynthetic process, beta-catenin-TCF complex assembly, and histone modification. These results indicate that MAPK mediates the aberrant expression of lncRNAs. LINC00941 is the lncRNA by MAPK most consistently promoted, and is implicated in the dismal prognosis of pancreatic cancer. MAPK-associated lncRNAs may play pivotal roles in malignant phenotypes of pancreatic cancer, and as such might represent both potentially valid therapeutic targets and diagnostic biomarkers.
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spelling pubmed-98189292023-01-07 Long Non-Coding RNAs Associated with Mitogen-Activated Protein Kinase in Human Pancreatic Cancer Ishikawa, Tomohiko Fukushige, Shinichi Saiki, Yuriko Hirose, Katsuya Hiyoshi, Takako Ogawa, Takenori Katori, Yukio Furukawa, Toru Cancers (Basel) Article SIMPLE SUMMARY: Long non-coding RNAs (lncRNAs) have emerged as a significant player in various cancers, including pancreatic cancer. However, how lncRNAs are aberrantly expressed in cancers is largely unknown. We hypothesized that lncRNAs would be regulated by signaling pathways and contribute to malignant phenotypes of cancer. In this study, to understand the significance of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) for the expression of lncRNAs in pancreatic cancer, we performed comparative transcriptome analyses between pancreatic cancer cell lines with or without activation of MAPK. We identified 45 lncRNAs presumably associated with MAPK in pancreatic cancer cells; among these, LINC00941 was consistently upregulated by MAPK. The promoter of LINC00941 was determined and found to be preferentially associated with MAPK activity via ETS-1 binding site. TCGA data analysis indicated that high expression of LINC00941 was associated with poor prognosis of pancreatic cancer patients. Downstream targets of LINC00941 were involved in 44 biological processes, including the glycoprotein biosynthetic process, beta-catenin-TCF complex assembly, and histone modification. These results indicate that MAPK mediates the aberrant expression of lncRNAs, and LINC00941 is the most consistently promoted lncRNA by MAPK in pancreatic cancer. Therefore, MAPK-associated lncRNAs might represent both potentially valid therapeutic targets and diagnostic biomarkers. ABSTRACT: Long non-coding RNAs (lncRNAs) have emerged as a significant player in various cancers, including pancreatic cancer. However, how lncRNAs are aberrantly expressed in cancers is largely unknown. We hypothesized that lncRNAs would be regulated by signaling pathways and contribute to malignant phenotypes of cancer. In this study, to understand the significance of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), which is a major aberrant signaling pathway in pancreatic cancer, for the expression of lncRNAs, we performed comparative transcriptome analyses between pancreatic cancer cell lines with or without activation of MAPK. We identified 45 lncRNAs presumably associated with MAPK in pancreatic cancer cells; among these, LINC00941 was consistently upregulated by MAPK. The immediate genomic upstream region flanking LINC00941 was identified as a promoter region, the activity of which was found to be preferentially associated with MAPK activity via ETS-1 binding site. LINC00941 promoted cell proliferation in vitro. Moreover, TCGA data analysis indicated that high expression of LINC00941 was associated with poor prognosis of patients with pancreatic cancer. Transcriptomes comparing transcriptions between cells with and without LINC00941 knockdown revealed 3229 differentially expressed genes involved in 44 biological processes, including the glycoprotein biosynthetic process, beta-catenin-TCF complex assembly, and histone modification. These results indicate that MAPK mediates the aberrant expression of lncRNAs. LINC00941 is the lncRNA by MAPK most consistently promoted, and is implicated in the dismal prognosis of pancreatic cancer. MAPK-associated lncRNAs may play pivotal roles in malignant phenotypes of pancreatic cancer, and as such might represent both potentially valid therapeutic targets and diagnostic biomarkers. MDPI 2023-01-02 /pmc/articles/PMC9818929/ /pubmed/36612299 http://dx.doi.org/10.3390/cancers15010303 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
Ishikawa, Tomohiko
Fukushige, Shinichi
Saiki, Yuriko
Hirose, Katsuya
Hiyoshi, Takako
Ogawa, Takenori
Katori, Yukio
Furukawa, Toru
Long Non-Coding RNAs Associated with Mitogen-Activated Protein Kinase in Human Pancreatic Cancer
title Long Non-Coding RNAs Associated with Mitogen-Activated Protein Kinase in Human Pancreatic Cancer
title_full Long Non-Coding RNAs Associated with Mitogen-Activated Protein Kinase in Human Pancreatic Cancer
title_fullStr Long Non-Coding RNAs Associated with Mitogen-Activated Protein Kinase in Human Pancreatic Cancer
title_full_unstemmed Long Non-Coding RNAs Associated with Mitogen-Activated Protein Kinase in Human Pancreatic Cancer
title_short Long Non-Coding RNAs Associated with Mitogen-Activated Protein Kinase in Human Pancreatic Cancer
title_sort long non-coding rnas associated with mitogen-activated protein kinase in human pancreatic cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818929/
https://www.ncbi.nlm.nih.gov/pubmed/36612299
http://dx.doi.org/10.3390/cancers15010303
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