circMSH3 is a potential biomarker for the diagnosis of colorectal cancer and affects the distant metastasis of colorectal cancer

Objectives To identify the most significantly differentially expressed circular RNAs (circRNAs) in colorectal cancer (CRC) tissues in terms of their expression levels and circularity, and to analyze the relationship between their expression levels and the clinical characteristics of patients. Method...

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Main Authors: Jian Shen, Yu Min, Jingen Luo, Xingkui Tang, Zeping Han, Wenfeng Luo, Fangmei Xie, Mingrong Cao, Taicheng Zhou, Jinhua He
Format: Article
Language:English
Published: PeerJ Inc. 2023-11-01
Series:PeerJ
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Online Access:https://peerj.com/articles/16297.pdf
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author Jian Shen
Yu Min
Jingen Luo
Xingkui Tang
Zeping Han
Wenfeng Luo
Fangmei Xie
Mingrong Cao
Taicheng Zhou
Jinhua He
author_facet Jian Shen
Yu Min
Jingen Luo
Xingkui Tang
Zeping Han
Wenfeng Luo
Fangmei Xie
Mingrong Cao
Taicheng Zhou
Jinhua He
author_sort Jian Shen
collection DOAJ
description Objectives To identify the most significantly differentially expressed circular RNAs (circRNAs) in colorectal cancer (CRC) tissues in terms of their expression levels and circularity, and to analyze the relationship between their expression levels and the clinical characteristics of patients. Methods circRNA RNA-seq technology was used to screen differentially expressed circRNAs in CRC. Sanger sequencing was used to identify circRNA back-splice junction sites. The relative expression levels of hsa_circ_0003761 (circMSH3) in CRC tissues and cell lines were detected by quantitative real-time fluorescence PCR technology. An RNA-protein pull-down assay was used to detect protein binding to circRNAs. Dual-luciferase reporter gene vectors were constructed to verify that circRNAs bind to microRNAs. Results Four hundred twenty circRNAs were found to be upregulated, and 616 circRNAs were downregulated. circMSH3 was derived from the MutS homolog 3 (MSH3) gene and was formed by a loop of exons 9, 10, 11, and 12. In 110 pairs of CRC and adjacent tissues, circMSH3 expression was 4.487-fold higher in CRC tissues. circMSH3 was also highly expressed in the HT-29 and LOVO CRC cell lines. The expression level of circMSH3 was associated with distant metastasis in CRC patients (P = 0.043); the area under the curve (AUC) of circMSH3 for CRC diagnosis was 0.75, with a sensitivity and specificity of 70.9% and 66.4%, respectively. circMSH3 could bind to a variety of proteins, mainly those involved in RNA transcription, splicing, cell cycle, and cell junctions. Furthermore, circMSH3 could bind to miR-1276, miR-942-5p, and miR-409-3p. Conclusion circMSH3 is a potential biomarker for the diagnosis of CRC and affects the distant metastasis of CRC. Multiple RNA-binding protein binds to circMSH3, and circMSH3 binds to miR-1276, miR-942-5p, and miR-409-3p, thereby affecting the expression of circMSH3.
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spelling doaj.art-a703b022f7744c1d946ff3b4c5d6a0be2023-12-03T11:53:25ZengPeerJ Inc.PeerJ2167-83592023-11-0111e1629710.7717/peerj.16297circMSH3 is a potential biomarker for the diagnosis of colorectal cancer and affects the distant metastasis of colorectal cancerJian Shen0Yu Min1Jingen Luo2Xingkui Tang3Zeping Han4Wenfeng Luo5Fangmei Xie6Mingrong Cao7Taicheng Zhou8Jinhua He9Department of Central Laboratory, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, ChinaGuangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaDepartment of General Surgery, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, ChinaDepartment of General Surgery, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, ChinaDepartment of Central Laboratory, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, ChinaDepartment of Central Laboratory, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, ChinaDepartment of Central Laboratory, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, ChinaDepartment of Gastroenterological Surgery and Hernia Center & Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of Central Laboratory, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, ChinaObjectives To identify the most significantly differentially expressed circular RNAs (circRNAs) in colorectal cancer (CRC) tissues in terms of their expression levels and circularity, and to analyze the relationship between their expression levels and the clinical characteristics of patients. Methods circRNA RNA-seq technology was used to screen differentially expressed circRNAs in CRC. Sanger sequencing was used to identify circRNA back-splice junction sites. The relative expression levels of hsa_circ_0003761 (circMSH3) in CRC tissues and cell lines were detected by quantitative real-time fluorescence PCR technology. An RNA-protein pull-down assay was used to detect protein binding to circRNAs. Dual-luciferase reporter gene vectors were constructed to verify that circRNAs bind to microRNAs. Results Four hundred twenty circRNAs were found to be upregulated, and 616 circRNAs were downregulated. circMSH3 was derived from the MutS homolog 3 (MSH3) gene and was formed by a loop of exons 9, 10, 11, and 12. In 110 pairs of CRC and adjacent tissues, circMSH3 expression was 4.487-fold higher in CRC tissues. circMSH3 was also highly expressed in the HT-29 and LOVO CRC cell lines. The expression level of circMSH3 was associated with distant metastasis in CRC patients (P = 0.043); the area under the curve (AUC) of circMSH3 for CRC diagnosis was 0.75, with a sensitivity and specificity of 70.9% and 66.4%, respectively. circMSH3 could bind to a variety of proteins, mainly those involved in RNA transcription, splicing, cell cycle, and cell junctions. Furthermore, circMSH3 could bind to miR-1276, miR-942-5p, and miR-409-3p. Conclusion circMSH3 is a potential biomarker for the diagnosis of CRC and affects the distant metastasis of CRC. Multiple RNA-binding protein binds to circMSH3, and circMSH3 binds to miR-1276, miR-942-5p, and miR-409-3p, thereby affecting the expression of circMSH3.https://peerj.com/articles/16297.pdfColorectal cancerHsa_circ_0003761CircMSH3RNA-protein pull-downMiR-1276MiR-942-5p
spellingShingle Jian Shen
Yu Min
Jingen Luo
Xingkui Tang
Zeping Han
Wenfeng Luo
Fangmei Xie
Mingrong Cao
Taicheng Zhou
Jinhua He
circMSH3 is a potential biomarker for the diagnosis of colorectal cancer and affects the distant metastasis of colorectal cancer
PeerJ
Colorectal cancer
Hsa_circ_0003761
CircMSH3
RNA-protein pull-down
MiR-1276
MiR-942-5p
title circMSH3 is a potential biomarker for the diagnosis of colorectal cancer and affects the distant metastasis of colorectal cancer
title_full circMSH3 is a potential biomarker for the diagnosis of colorectal cancer and affects the distant metastasis of colorectal cancer
title_fullStr circMSH3 is a potential biomarker for the diagnosis of colorectal cancer and affects the distant metastasis of colorectal cancer
title_full_unstemmed circMSH3 is a potential biomarker for the diagnosis of colorectal cancer and affects the distant metastasis of colorectal cancer
title_short circMSH3 is a potential biomarker for the diagnosis of colorectal cancer and affects the distant metastasis of colorectal cancer
title_sort circmsh3 is a potential biomarker for the diagnosis of colorectal cancer and affects the distant metastasis of colorectal cancer
topic Colorectal cancer
Hsa_circ_0003761
CircMSH3
RNA-protein pull-down
MiR-1276
MiR-942-5p
url https://peerj.com/articles/16297.pdf
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