Construction of miRNA-mRNA-TF Regulatory Network for Diagnosis of Gastric Cancer

Gastric cancer (GC), as an epidemic cancer worldwide, has more than 1 million new cases and an estimated 769,000 deaths worldwide in 2020, ranking fifth and fourth in global morbidity and mortality. In mammals, both miRNAs and transcription factors (TFs) play a partial role in gene expression regula...

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Autores principales:	Zhenjie Fu, Yuqin Xu, Yan Chen, Hang Lv, Guiping Chen, Yitao Chen
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/fdd2fdfef93440c2b7cf1e5a8b760caa
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spelling	oai:doaj.org-article:fdd2fdfef93440c2b7cf1e5a8b760caa2021-11-29T00:56:59ZConstruction of miRNA-mRNA-TF Regulatory Network for Diagnosis of Gastric Cancer2314-614110.1155/2021/9121478https://doaj.org/article/fdd2fdfef93440c2b7cf1e5a8b760caa2021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/9121478https://doaj.org/toc/2314-6141Gastric cancer (GC), as an epidemic cancer worldwide, has more than 1 million new cases and an estimated 769,000 deaths worldwide in 2020, ranking fifth and fourth in global morbidity and mortality. In mammals, both miRNAs and transcription factors (TFs) play a partial role in gene expression regulation. The mRNA expression profile and miRNA expression profile of GEO database were screened by GEO2R for differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs). Then, DAVID annotated the functions of DEGs to understand the functions played in biological processes. The prediction of potential target genes of miRNA and key TFs of mRNA was performed by mipathDB V2.0 and CHEA3, respectively, and the gene list comparison was performed to look for overlapping genes coregulated by key TFs and DEMs. Finally, the obtained miRNAs, TF, and overlapping genes were used to construct the miRNA-mRNA-TF regulatory network, which was verified by RT-qPCR. 76 upregulated DEGs, 199 downregulated DEGs, and 3 upregulated miRNAs (miR-199a-3p/miR-199b-3p, miR-125b-5p, and miR-199a-5p) were identified from the expression profiles of mRNA (GSE26899, GSE29998, GSE51575, and GSE13911) and miRNA (GSE93415), respectively. Through database prediction and gene list comparison, it was found that among the 199 downregulated DEGs, 61, 71, and 69 genes were the potential targets of miR-199a-3p/miR-199b-3p, miR-125b-5p, and miR-199a-5p, respectively. 199 downregulated DEGs were used as the gene list for the prediction of key TFs, and the results showed that RFX6 ranked the highest. The potential target overlap genes of miR-199a-3p/miR-199b-3p, miR-125b-5p, and miR-199a-5p were 4 genes (SH3GL2, ATP4B, CTSE, and SORBS2), 7 genes (SLC7A8, RNASE4, ESRRG, PGC, MUC6, Fam3B, and FMO5), and 6 genes (CHGA, PDK4, TMPRSS2, CLIC6, GPX3, and PSCA), respectively. Finally, we constructed a miRNA-mRNA-TF regulatory network based on the above 17 mRNAs, 3 miRNAs, and 1 TF and verified by RT-qPCR and western blot results that the expression of RFX6 was downregulated in GC tissues. These identified miRNAs, mRNAs, and TF have a certain reference value for further exploration of the regulatory mechanism of GC.Zhenjie FuYuqin XuYan ChenHang LvGuiping ChenYitao ChenHindawi LimitedarticleMedicineRENBioMed Research International, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Zhenjie Fu Yuqin Xu Yan Chen Hang Lv Guiping Chen Yitao Chen Construction of miRNA-mRNA-TF Regulatory Network for Diagnosis of Gastric Cancer
description	Gastric cancer (GC), as an epidemic cancer worldwide, has more than 1 million new cases and an estimated 769,000 deaths worldwide in 2020, ranking fifth and fourth in global morbidity and mortality. In mammals, both miRNAs and transcription factors (TFs) play a partial role in gene expression regulation. The mRNA expression profile and miRNA expression profile of GEO database were screened by GEO2R for differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs). Then, DAVID annotated the functions of DEGs to understand the functions played in biological processes. The prediction of potential target genes of miRNA and key TFs of mRNA was performed by mipathDB V2.0 and CHEA3, respectively, and the gene list comparison was performed to look for overlapping genes coregulated by key TFs and DEMs. Finally, the obtained miRNAs, TF, and overlapping genes were used to construct the miRNA-mRNA-TF regulatory network, which was verified by RT-qPCR. 76 upregulated DEGs, 199 downregulated DEGs, and 3 upregulated miRNAs (miR-199a-3p/miR-199b-3p, miR-125b-5p, and miR-199a-5p) were identified from the expression profiles of mRNA (GSE26899, GSE29998, GSE51575, and GSE13911) and miRNA (GSE93415), respectively. Through database prediction and gene list comparison, it was found that among the 199 downregulated DEGs, 61, 71, and 69 genes were the potential targets of miR-199a-3p/miR-199b-3p, miR-125b-5p, and miR-199a-5p, respectively. 199 downregulated DEGs were used as the gene list for the prediction of key TFs, and the results showed that RFX6 ranked the highest. The potential target overlap genes of miR-199a-3p/miR-199b-3p, miR-125b-5p, and miR-199a-5p were 4 genes (SH3GL2, ATP4B, CTSE, and SORBS2), 7 genes (SLC7A8, RNASE4, ESRRG, PGC, MUC6, Fam3B, and FMO5), and 6 genes (CHGA, PDK4, TMPRSS2, CLIC6, GPX3, and PSCA), respectively. Finally, we constructed a miRNA-mRNA-TF regulatory network based on the above 17 mRNAs, 3 miRNAs, and 1 TF and verified by RT-qPCR and western blot results that the expression of RFX6 was downregulated in GC tissues. These identified miRNAs, mRNAs, and TF have a certain reference value for further exploration of the regulatory mechanism of GC.
format	article
author	Zhenjie Fu Yuqin Xu Yan Chen Hang Lv Guiping Chen Yitao Chen
author_facet	Zhenjie Fu Yuqin Xu Yan Chen Hang Lv Guiping Chen Yitao Chen
author_sort	Zhenjie Fu
title	Construction of miRNA-mRNA-TF Regulatory Network for Diagnosis of Gastric Cancer
title_short	Construction of miRNA-mRNA-TF Regulatory Network for Diagnosis of Gastric Cancer
title_full	Construction of miRNA-mRNA-TF Regulatory Network for Diagnosis of Gastric Cancer
title_fullStr	Construction of miRNA-mRNA-TF Regulatory Network for Diagnosis of Gastric Cancer
title_full_unstemmed	Construction of miRNA-mRNA-TF Regulatory Network for Diagnosis of Gastric Cancer
title_sort	construction of mirna-mrna-tf regulatory network for diagnosis of gastric cancer
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/fdd2fdfef93440c2b7cf1e5a8b760caa
work_keys_str_mv	AT zhenjiefu constructionofmirnamrnatfregulatorynetworkfordiagnosisofgastriccancer AT yuqinxu constructionofmirnamrnatfregulatorynetworkfordiagnosisofgastriccancer AT yanchen constructionofmirnamrnatfregulatorynetworkfordiagnosisofgastriccancer AT hanglv constructionofmirnamrnatfregulatorynetworkfordiagnosisofgastriccancer AT guipingchen constructionofmirnamrnatfregulatorynetworkfordiagnosisofgastriccancer AT yitaochen constructionofmirnamrnatfregulatorynetworkfordiagnosisofgastriccancer
_version_	1718407686353059840

Construction of miRNA-mRNA-TF Regulatory Network for Diagnosis of Gastric Cancer

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