Genome‐wide analysis of mRNA and microRNA expression in colorectal cancer and adjacent normal mucosa

Abstract mRNA expression varies in human cancers. Such altered mRNA expression is negatively regulated by the expression of microRNAs (miRNAs), which play an important role in human tumorigenesis. According to this theory, inverse mRNA/miRNA expression may be a direct driver of cancer development, a...

Full description

Bibliographic Details
Main Authors: Yuma Ito, Mitsumasa Osakabe, Takeshi Niinuma, Noriyuki Uesugi, Ryo Sugimoto, Naoki Yanagawa, Koki Otsuka, Akira Sasaki, Takayuki Matsumoto, Hiromu Suzuki, Tamotsu Sugai
Format: Article
Language:English
Published: Wiley 2022-07-01
Series:The Journal of Pathology: Clinical Research
Subjects:
Online Access:https://doi.org/10.1002/cjp2.268
_version_ 1818218847266668544
author Yuma Ito
Mitsumasa Osakabe
Takeshi Niinuma
Noriyuki Uesugi
Ryo Sugimoto
Naoki Yanagawa
Koki Otsuka
Akira Sasaki
Takayuki Matsumoto
Hiromu Suzuki
Tamotsu Sugai
author_facet Yuma Ito
Mitsumasa Osakabe
Takeshi Niinuma
Noriyuki Uesugi
Ryo Sugimoto
Naoki Yanagawa
Koki Otsuka
Akira Sasaki
Takayuki Matsumoto
Hiromu Suzuki
Tamotsu Sugai
author_sort Yuma Ito
collection DOAJ
description Abstract mRNA expression varies in human cancers. Such altered mRNA expression is negatively regulated by the expression of microRNAs (miRNAs), which play an important role in human tumorigenesis. According to this theory, inverse mRNA/miRNA expression may be a direct driver of cancer development, and certain genetic events may occur prior to the development of any discernible histological abnormalities. We examined the inverse expression between mRNAs and their corresponding miRNAs in colorectal cancer (CRC) and adjacent normal mucosa and performed pathway analysis to identify mRNA/miRNA networks. The cancer samples were divided into first (20 cases) and second (24 cases) cohorts, and 48 samples were obtained from two sections of the normal mucosa adjacent to the tumors from the second cohort. We investigated mRNAs with commonly altered expression in CRC and adjacent normal mucosa using isolated cancer glands and normal crypts from the first cohort, compared with that of distal normal crypts, using an array‐based method. As a result, significant inverse correlations between CEACAM1 and miRNA‐7114‐5p and between AK1 and miRNA‐6780‐5p were found in CRC and adjacent normal mucosa. We validated these correlations in the second cohort using RT‐PCR. To confirm these findings, transfection and immunohistochemical assays were also performed, which verified the inverse correlation between CEACAM1 and miRNA‐7114‐5p. Our findings suggest that the inverse correlations between the CEACAM1/miRNA‐7114‐5p and possibly AK1/miRNA‐6780‐5p pairs play an important role in early CRC development, and may help identify potential molecular targets for early detection of CRC.
first_indexed 2024-12-12T07:30:16Z
format Article
id doaj.art-39bbf9054c6545f780908a93806d834b
institution Directory Open Access Journal
issn 2056-4538
language English
last_indexed 2024-12-12T07:30:16Z
publishDate 2022-07-01
publisher Wiley
record_format Article
series The Journal of Pathology: Clinical Research
spelling doaj.art-39bbf9054c6545f780908a93806d834b2022-12-22T00:33:03ZengWileyThe Journal of Pathology: Clinical Research2056-45382022-07-018431332610.1002/cjp2.268Genome‐wide analysis of mRNA and microRNA expression in colorectal cancer and adjacent normal mucosaYuma Ito0Mitsumasa Osakabe1Takeshi Niinuma2Noriyuki Uesugi3Ryo Sugimoto4Naoki Yanagawa5Koki Otsuka6Akira Sasaki7Takayuki Matsumoto8Hiromu Suzuki9Tamotsu Sugai10Department of Molecular Diagnostic Pathology, School of Medicine Iwate Medical University Yahaba JapanDepartment of Molecular Diagnostic Pathology, School of Medicine Iwate Medical University Yahaba JapanDepartment of Molecular Biology School of Medicine, Sapporo Medical University Sapporo JapanDepartment of Molecular Diagnostic Pathology, School of Medicine Iwate Medical University Yahaba JapanDepartment of Molecular Diagnostic Pathology, School of Medicine Iwate Medical University Yahaba JapanDepartment of Molecular Diagnostic Pathology, School of Medicine Iwate Medical University Yahaba JapanDepartment of Surgery, School of Medicine Iwate Medical University Yahaba JapanDepartment of Surgery, School of Medicine Iwate Medical University Yahaba JapanDivision of Gastroenterology, Department of Internal Medicine Iwate Medical University Yahaba JapanDepartment of Molecular Biology School of Medicine, Sapporo Medical University Sapporo JapanDepartment of Molecular Diagnostic Pathology, School of Medicine Iwate Medical University Yahaba JapanAbstract mRNA expression varies in human cancers. Such altered mRNA expression is negatively regulated by the expression of microRNAs (miRNAs), which play an important role in human tumorigenesis. According to this theory, inverse mRNA/miRNA expression may be a direct driver of cancer development, and certain genetic events may occur prior to the development of any discernible histological abnormalities. We examined the inverse expression between mRNAs and their corresponding miRNAs in colorectal cancer (CRC) and adjacent normal mucosa and performed pathway analysis to identify mRNA/miRNA networks. The cancer samples were divided into first (20 cases) and second (24 cases) cohorts, and 48 samples were obtained from two sections of the normal mucosa adjacent to the tumors from the second cohort. We investigated mRNAs with commonly altered expression in CRC and adjacent normal mucosa using isolated cancer glands and normal crypts from the first cohort, compared with that of distal normal crypts, using an array‐based method. As a result, significant inverse correlations between CEACAM1 and miRNA‐7114‐5p and between AK1 and miRNA‐6780‐5p were found in CRC and adjacent normal mucosa. We validated these correlations in the second cohort using RT‐PCR. To confirm these findings, transfection and immunohistochemical assays were also performed, which verified the inverse correlation between CEACAM1 and miRNA‐7114‐5p. Our findings suggest that the inverse correlations between the CEACAM1/miRNA‐7114‐5p and possibly AK1/miRNA‐6780‐5p pairs play an important role in early CRC development, and may help identify potential molecular targets for early detection of CRC.https://doi.org/10.1002/cjp2.268adjacent normal mucosaarray‐based analysiscolorectal cancermicroRNAmRNA
spellingShingle Yuma Ito
Mitsumasa Osakabe
Takeshi Niinuma
Noriyuki Uesugi
Ryo Sugimoto
Naoki Yanagawa
Koki Otsuka
Akira Sasaki
Takayuki Matsumoto
Hiromu Suzuki
Tamotsu Sugai
Genome‐wide analysis of mRNA and microRNA expression in colorectal cancer and adjacent normal mucosa
The Journal of Pathology: Clinical Research
adjacent normal mucosa
array‐based analysis
colorectal cancer
microRNA
mRNA
title Genome‐wide analysis of mRNA and microRNA expression in colorectal cancer and adjacent normal mucosa
title_full Genome‐wide analysis of mRNA and microRNA expression in colorectal cancer and adjacent normal mucosa
title_fullStr Genome‐wide analysis of mRNA and microRNA expression in colorectal cancer and adjacent normal mucosa
title_full_unstemmed Genome‐wide analysis of mRNA and microRNA expression in colorectal cancer and adjacent normal mucosa
title_short Genome‐wide analysis of mRNA and microRNA expression in colorectal cancer and adjacent normal mucosa
title_sort genome wide analysis of mrna and microrna expression in colorectal cancer and adjacent normal mucosa
topic adjacent normal mucosa
array‐based analysis
colorectal cancer
microRNA
mRNA
url https://doi.org/10.1002/cjp2.268
work_keys_str_mv AT yumaito genomewideanalysisofmrnaandmicrornaexpressionincolorectalcancerandadjacentnormalmucosa
AT mitsumasaosakabe genomewideanalysisofmrnaandmicrornaexpressionincolorectalcancerandadjacentnormalmucosa
AT takeshiniinuma genomewideanalysisofmrnaandmicrornaexpressionincolorectalcancerandadjacentnormalmucosa
AT noriyukiuesugi genomewideanalysisofmrnaandmicrornaexpressionincolorectalcancerandadjacentnormalmucosa
AT ryosugimoto genomewideanalysisofmrnaandmicrornaexpressionincolorectalcancerandadjacentnormalmucosa
AT naokiyanagawa genomewideanalysisofmrnaandmicrornaexpressionincolorectalcancerandadjacentnormalmucosa
AT kokiotsuka genomewideanalysisofmrnaandmicrornaexpressionincolorectalcancerandadjacentnormalmucosa
AT akirasasaki genomewideanalysisofmrnaandmicrornaexpressionincolorectalcancerandadjacentnormalmucosa
AT takayukimatsumoto genomewideanalysisofmrnaandmicrornaexpressionincolorectalcancerandadjacentnormalmucosa
AT hiromusuzuki genomewideanalysisofmrnaandmicrornaexpressionincolorectalcancerandadjacentnormalmucosa
AT tamotsusugai genomewideanalysisofmrnaandmicrornaexpressionincolorectalcancerandadjacentnormalmucosa