Cargando…
Genome-Wide Analysis of microRNA and mRNA Expression in Colorectal Intramucosal Neoplasia and Colorectal Cancer With a Microsatellite-Stable Phenotype Based on Adenoma-Carcinoma Sequences
BACKGROUND: Although MicroRNAs (miRNAs) play important roles in various biological processes, the biological functions of miRNAs are achieved through mRNAs. The aim of this study is to identify dysregulated miRNA/mRNA expression patterns in colorectal tumors. METHODS: We examined 42 colorectal tumor...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300861/ https://www.ncbi.nlm.nih.gov/pubmed/35875068 http://dx.doi.org/10.3389/fonc.2022.831100 |
_version_ | 1784751304088748032 |
---|---|
author | Sugai, Tamotsu Osakabe, Mitsumasa Niinuma, Takeshi Sugimoto, Ryo Eizuka, Makoto Tanaka, Yoshihito Yanagawa, Naoki Otsuka, Koki Sasaki, Akira Matsumoto, Takayuki Suzuki, Hiromu |
author_facet | Sugai, Tamotsu Osakabe, Mitsumasa Niinuma, Takeshi Sugimoto, Ryo Eizuka, Makoto Tanaka, Yoshihito Yanagawa, Naoki Otsuka, Koki Sasaki, Akira Matsumoto, Takayuki Suzuki, Hiromu |
author_sort | Sugai, Tamotsu |
collection | PubMed |
description | BACKGROUND: Although MicroRNAs (miRNAs) play important roles in various biological processes, the biological functions of miRNAs are achieved through mRNAs. The aim of this study is to identify dysregulated miRNA/mRNA expression patterns in colorectal tumors. METHODS: We examined 42 colorectal tumors [15 adenomas, 8 intramucosal cancers (IMCs), and 19 invasive colorectal cancers (CRCs)] with the microsatellite stable (MSS) phenotype (first cohort). The first cohort was used for genome-wide miRNA and mRNA expression arrays, whereas the second cohort (37 colorectal neoplasias) was used for validation analyses. Finally, we used 15 cases of “adenoma in/with carcinoma” to identify network patterns of miRNAs/mRNAs that were directly associated with neoplastic progression. In addition, simple regression analysis for array-based and RT-PCR analyses was performed to select candidate miRNA–mRNA pairs. Transfection of miRNA mimics was also performed to confirm whether target mRNA expression is affected by specific miRNAs. RESULTS: Specific paired miRNA/mRNA networks, including hsa-miR-34a-5p/SLC12A2, hsa-miR-15b-5p/SLC12A2, hsa-miR-195-5p/SLC12A2, hsa-miRNA-502-3p/OLFM4, hsa-miRNA-6807-5p/ZG16, and hsa-miRNA 3064-5p/SH3BGRL3, were identified in samples of adenoma, IMC, and CRC with the MSS phenotype. In adenomatous lesions obtained from the same tumor with a carcinomatous lesion, we identified pairs of miRNA-130a-3p/HSPA8 and miRNA-22-3p/RP53 that were linked to multiple pathways. On the other hand, 2 pairs of miRNA/mRNA (miRNA-660-5p and miRNA-664a-5p/APP) were found in isolated carcinomatous glands. Ectopic expression of miRNA 3064-5p suppressed SH3BGRL3 expression. CONCLUSIONS: We found that networks based on specific pairs of miRNAs/mRNAs contribute to progression from adenomatous and carcinomatous lesions. Our results provide insights into the molecular tumorigenesis of colorectal tumors. |
format | Online Article Text |
id | pubmed-9300861 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93008612022-07-22 Genome-Wide Analysis of microRNA and mRNA Expression in Colorectal Intramucosal Neoplasia and Colorectal Cancer With a Microsatellite-Stable Phenotype Based on Adenoma-Carcinoma Sequences Sugai, Tamotsu Osakabe, Mitsumasa Niinuma, Takeshi Sugimoto, Ryo Eizuka, Makoto Tanaka, Yoshihito Yanagawa, Naoki Otsuka, Koki Sasaki, Akira Matsumoto, Takayuki Suzuki, Hiromu Front Oncol Oncology BACKGROUND: Although MicroRNAs (miRNAs) play important roles in various biological processes, the biological functions of miRNAs are achieved through mRNAs. The aim of this study is to identify dysregulated miRNA/mRNA expression patterns in colorectal tumors. METHODS: We examined 42 colorectal tumors [15 adenomas, 8 intramucosal cancers (IMCs), and 19 invasive colorectal cancers (CRCs)] with the microsatellite stable (MSS) phenotype (first cohort). The first cohort was used for genome-wide miRNA and mRNA expression arrays, whereas the second cohort (37 colorectal neoplasias) was used for validation analyses. Finally, we used 15 cases of “adenoma in/with carcinoma” to identify network patterns of miRNAs/mRNAs that were directly associated with neoplastic progression. In addition, simple regression analysis for array-based and RT-PCR analyses was performed to select candidate miRNA–mRNA pairs. Transfection of miRNA mimics was also performed to confirm whether target mRNA expression is affected by specific miRNAs. RESULTS: Specific paired miRNA/mRNA networks, including hsa-miR-34a-5p/SLC12A2, hsa-miR-15b-5p/SLC12A2, hsa-miR-195-5p/SLC12A2, hsa-miRNA-502-3p/OLFM4, hsa-miRNA-6807-5p/ZG16, and hsa-miRNA 3064-5p/SH3BGRL3, were identified in samples of adenoma, IMC, and CRC with the MSS phenotype. In adenomatous lesions obtained from the same tumor with a carcinomatous lesion, we identified pairs of miRNA-130a-3p/HSPA8 and miRNA-22-3p/RP53 that were linked to multiple pathways. On the other hand, 2 pairs of miRNA/mRNA (miRNA-660-5p and miRNA-664a-5p/APP) were found in isolated carcinomatous glands. Ectopic expression of miRNA 3064-5p suppressed SH3BGRL3 expression. CONCLUSIONS: We found that networks based on specific pairs of miRNAs/mRNAs contribute to progression from adenomatous and carcinomatous lesions. Our results provide insights into the molecular tumorigenesis of colorectal tumors. Frontiers Media S.A. 2022-07-07 /pmc/articles/PMC9300861/ /pubmed/35875068 http://dx.doi.org/10.3389/fonc.2022.831100 Text en Copyright © 2022 Sugai, Osakabe, Niinuma, Sugimoto, Eizuka, Tanaka, Yanagawa, Otsuka, Sasaki, Matsumoto and Suzuki 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 | Oncology Sugai, Tamotsu Osakabe, Mitsumasa Niinuma, Takeshi Sugimoto, Ryo Eizuka, Makoto Tanaka, Yoshihito Yanagawa, Naoki Otsuka, Koki Sasaki, Akira Matsumoto, Takayuki Suzuki, Hiromu Genome-Wide Analysis of microRNA and mRNA Expression in Colorectal Intramucosal Neoplasia and Colorectal Cancer With a Microsatellite-Stable Phenotype Based on Adenoma-Carcinoma Sequences |
title | Genome-Wide Analysis of microRNA and mRNA Expression in Colorectal Intramucosal Neoplasia and Colorectal Cancer With a Microsatellite-Stable Phenotype Based on Adenoma-Carcinoma Sequences |
title_full | Genome-Wide Analysis of microRNA and mRNA Expression in Colorectal Intramucosal Neoplasia and Colorectal Cancer With a Microsatellite-Stable Phenotype Based on Adenoma-Carcinoma Sequences |
title_fullStr | Genome-Wide Analysis of microRNA and mRNA Expression in Colorectal Intramucosal Neoplasia and Colorectal Cancer With a Microsatellite-Stable Phenotype Based on Adenoma-Carcinoma Sequences |
title_full_unstemmed | Genome-Wide Analysis of microRNA and mRNA Expression in Colorectal Intramucosal Neoplasia and Colorectal Cancer With a Microsatellite-Stable Phenotype Based on Adenoma-Carcinoma Sequences |
title_short | Genome-Wide Analysis of microRNA and mRNA Expression in Colorectal Intramucosal Neoplasia and Colorectal Cancer With a Microsatellite-Stable Phenotype Based on Adenoma-Carcinoma Sequences |
title_sort | genome-wide analysis of microrna and mrna expression in colorectal intramucosal neoplasia and colorectal cancer with a microsatellite-stable phenotype based on adenoma-carcinoma sequences |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300861/ https://www.ncbi.nlm.nih.gov/pubmed/35875068 http://dx.doi.org/10.3389/fonc.2022.831100 |
work_keys_str_mv | AT sugaitamotsu genomewideanalysisofmicrornaandmrnaexpressionincolorectalintramucosalneoplasiaandcolorectalcancerwithamicrosatellitestablephenotypebasedonadenomacarcinomasequences AT osakabemitsumasa genomewideanalysisofmicrornaandmrnaexpressionincolorectalintramucosalneoplasiaandcolorectalcancerwithamicrosatellitestablephenotypebasedonadenomacarcinomasequences AT niinumatakeshi genomewideanalysisofmicrornaandmrnaexpressionincolorectalintramucosalneoplasiaandcolorectalcancerwithamicrosatellitestablephenotypebasedonadenomacarcinomasequences AT sugimotoryo genomewideanalysisofmicrornaandmrnaexpressionincolorectalintramucosalneoplasiaandcolorectalcancerwithamicrosatellitestablephenotypebasedonadenomacarcinomasequences AT eizukamakoto genomewideanalysisofmicrornaandmrnaexpressionincolorectalintramucosalneoplasiaandcolorectalcancerwithamicrosatellitestablephenotypebasedonadenomacarcinomasequences AT tanakayoshihito genomewideanalysisofmicrornaandmrnaexpressionincolorectalintramucosalneoplasiaandcolorectalcancerwithamicrosatellitestablephenotypebasedonadenomacarcinomasequences AT yanagawanaoki genomewideanalysisofmicrornaandmrnaexpressionincolorectalintramucosalneoplasiaandcolorectalcancerwithamicrosatellitestablephenotypebasedonadenomacarcinomasequences AT otsukakoki genomewideanalysisofmicrornaandmrnaexpressionincolorectalintramucosalneoplasiaandcolorectalcancerwithamicrosatellitestablephenotypebasedonadenomacarcinomasequences AT sasakiakira genomewideanalysisofmicrornaandmrnaexpressionincolorectalintramucosalneoplasiaandcolorectalcancerwithamicrosatellitestablephenotypebasedonadenomacarcinomasequences AT matsumototakayuki genomewideanalysisofmicrornaandmrnaexpressionincolorectalintramucosalneoplasiaandcolorectalcancerwithamicrosatellitestablephenotypebasedonadenomacarcinomasequences AT suzukihiromu genomewideanalysisofmicrornaandmrnaexpressionincolorectalintramucosalneoplasiaandcolorectalcancerwithamicrosatellitestablephenotypebasedonadenomacarcinomasequences |