Somatic Copy Number Alterations in Colorectal Cancer Lead to a Differentially Expressed ceRNA Network (ceRNet)

Colorectal cancer (CRC) represents the second deadliest malignancy worldwide. Around 75% of CRC patients exhibit high levels of chromosome instability that result in the accumulation of somatic copy number alterations. These alterations are associated with the amplification of oncogenes and deletion...

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Main Authors: Héctor Herrera-Orozco, Verónica García-Castillo, Eduardo López-Urrutia, Antonio Daniel Martinez-Gutierrez, Eloy Pérez-Yepez, Oliver Millán-Catalán, David Cantú de León, César López-Camarillo, Nadia J. Jacobo-Herrera, Mauricio Rodríguez-Dorantes, Rosalío Ramos-Payán, Carlos Pérez-Plasencia
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:Current Issues in Molecular Biology
Subjects:
Online Access:https://www.mdpi.com/1467-3045/45/12/597
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author Héctor Herrera-Orozco
Verónica García-Castillo
Eduardo López-Urrutia
Antonio Daniel Martinez-Gutierrez
Eloy Pérez-Yepez
Oliver Millán-Catalán
David Cantú de León
César López-Camarillo
Nadia J. Jacobo-Herrera
Mauricio Rodríguez-Dorantes
Rosalío Ramos-Payán
Carlos Pérez-Plasencia
author_facet Héctor Herrera-Orozco
Verónica García-Castillo
Eduardo López-Urrutia
Antonio Daniel Martinez-Gutierrez
Eloy Pérez-Yepez
Oliver Millán-Catalán
David Cantú de León
César López-Camarillo
Nadia J. Jacobo-Herrera
Mauricio Rodríguez-Dorantes
Rosalío Ramos-Payán
Carlos Pérez-Plasencia
author_sort Héctor Herrera-Orozco
collection DOAJ
description Colorectal cancer (CRC) represents the second deadliest malignancy worldwide. Around 75% of CRC patients exhibit high levels of chromosome instability that result in the accumulation of somatic copy number alterations. These alterations are associated with the amplification of oncogenes and deletion of tumor-ppressor genes and contribute to the tumoral phenotype in different malignancies. Even though this relationship is well known, much remains to be investigated regarding the effect of said alterations in long non-coding RNAs (lncRNAs) and, in turn, the impact these alterations have on the tumor phenotype. The present study aimed to evaluate the role of differentially expressed lncRNAs coded in regions with copy number alterations in colorectal cancer patient samples. We downloaded RNA-seq files of the Colorectal Adenocarcinoma Project from the The Cancer Genome Atlas (TCGA) repository (285 sequenced tumor tissues and 41 non-tumor tissues), evaluated differential expression, and mapped them over genome sequencing data with regions presenting copy number alterations. We obtained 78 differentially expressed (LFC > 1|< −1, padj < 0.05) lncRNAs, 410 miRNAs, and 5028 mRNAs and constructed a competing endogenous RNA (ceRNA) network, predicting significant lncRNA–miRNA–mRNA interactions. Said network consisted of 30 lncRNAs, 19 miRNAs, and 77 mRNAs. To understand the role that our ceRNA network played, we performed KEGG and GO analysis and found several oncogenic and anti-oncogenic processes enriched by the molecular players in our network. Finally, to evaluate the clinical relevance of the lncRNA expression, we performed survival analysis and found that C5orf64, HOTAIR, and RRN3P3 correlated with overall patient survival. Our results showed that lncRNAs coded in regions affected by SCNAs form a complex gene regulatory network in CCR.
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spelling doaj.art-b1802939daaf41058e4b16337465248c2023-12-22T14:00:37ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452023-11-0145129549956510.3390/cimb45120597Somatic Copy Number Alterations in Colorectal Cancer Lead to a Differentially Expressed ceRNA Network (ceRNet)Héctor Herrera-Orozco0Verónica García-Castillo1Eduardo López-Urrutia2Antonio Daniel Martinez-Gutierrez3Eloy Pérez-Yepez4Oliver Millán-Catalán5David Cantú de León6César López-Camarillo7Nadia J. Jacobo-Herrera8Mauricio Rodríguez-Dorantes9Rosalío Ramos-Payán10Carlos Pérez-Plasencia11Laboratorio de Genómica, FES-Iztacala, Universidad Nacional Autónoma de México. Av. De los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, MexicoLaboratorio de Genómica, FES-Iztacala, Universidad Nacional Autónoma de México. Av. De los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, MexicoLaboratorio de Genómica, FES-Iztacala, Universidad Nacional Autónoma de México. Av. De los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, MexicoLaboratorio de Genómica, Instituto Nacional de Cancerología, Av. San Fernando 22, Tlalpan, Mexico City 14080, MexicoLaboratorio de Genómica, Instituto Nacional de Cancerología, Av. San Fernando 22, Tlalpan, Mexico City 14080, MexicoLaboratorio de Genómica, Instituto Nacional de Cancerología, Av. San Fernando 22, Tlalpan, Mexico City 14080, MexicoLaboratorio de Genómica, Instituto Nacional de Cancerología, Av. San Fernando 22, Tlalpan, Mexico City 14080, MexicoPosgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Calle Dr. García Diego 168, Cuauhtémoc, Mexico City 06720, MexicoUnidad de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Av. Vasco de Quiroga 15, Tlalpan, Mexico City 14080, MexicoLaboratorio de Oncogenómica, Instituto Nacional de Medicina Genómica, Tlalpan, Mexico City 14610, MexicoFaculty of Chemical and Biological Sciences, Autonomous University of Sinaloa, Culiacan 80030, MexicoLaboratorio de Genómica, FES-Iztacala, Universidad Nacional Autónoma de México. Av. De los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, MexicoColorectal cancer (CRC) represents the second deadliest malignancy worldwide. Around 75% of CRC patients exhibit high levels of chromosome instability that result in the accumulation of somatic copy number alterations. These alterations are associated with the amplification of oncogenes and deletion of tumor-ppressor genes and contribute to the tumoral phenotype in different malignancies. Even though this relationship is well known, much remains to be investigated regarding the effect of said alterations in long non-coding RNAs (lncRNAs) and, in turn, the impact these alterations have on the tumor phenotype. The present study aimed to evaluate the role of differentially expressed lncRNAs coded in regions with copy number alterations in colorectal cancer patient samples. We downloaded RNA-seq files of the Colorectal Adenocarcinoma Project from the The Cancer Genome Atlas (TCGA) repository (285 sequenced tumor tissues and 41 non-tumor tissues), evaluated differential expression, and mapped them over genome sequencing data with regions presenting copy number alterations. We obtained 78 differentially expressed (LFC > 1|< −1, padj < 0.05) lncRNAs, 410 miRNAs, and 5028 mRNAs and constructed a competing endogenous RNA (ceRNA) network, predicting significant lncRNA–miRNA–mRNA interactions. Said network consisted of 30 lncRNAs, 19 miRNAs, and 77 mRNAs. To understand the role that our ceRNA network played, we performed KEGG and GO analysis and found several oncogenic and anti-oncogenic processes enriched by the molecular players in our network. Finally, to evaluate the clinical relevance of the lncRNA expression, we performed survival analysis and found that C5orf64, HOTAIR, and RRN3P3 correlated with overall patient survival. Our results showed that lncRNAs coded in regions affected by SCNAs form a complex gene regulatory network in CCR.https://www.mdpi.com/1467-3045/45/12/597colorectal cancersomatic copy number alterationslong non-coding RNAscompetitive endogenous RNA (ceRNA) network
spellingShingle Héctor Herrera-Orozco
Verónica García-Castillo
Eduardo López-Urrutia
Antonio Daniel Martinez-Gutierrez
Eloy Pérez-Yepez
Oliver Millán-Catalán
David Cantú de León
César López-Camarillo
Nadia J. Jacobo-Herrera
Mauricio Rodríguez-Dorantes
Rosalío Ramos-Payán
Carlos Pérez-Plasencia
Somatic Copy Number Alterations in Colorectal Cancer Lead to a Differentially Expressed ceRNA Network (ceRNet)
Current Issues in Molecular Biology
colorectal cancer
somatic copy number alterations
long non-coding RNAs
competitive endogenous RNA (ceRNA) network
title Somatic Copy Number Alterations in Colorectal Cancer Lead to a Differentially Expressed ceRNA Network (ceRNet)
title_full Somatic Copy Number Alterations in Colorectal Cancer Lead to a Differentially Expressed ceRNA Network (ceRNet)
title_fullStr Somatic Copy Number Alterations in Colorectal Cancer Lead to a Differentially Expressed ceRNA Network (ceRNet)
title_full_unstemmed Somatic Copy Number Alterations in Colorectal Cancer Lead to a Differentially Expressed ceRNA Network (ceRNet)
title_short Somatic Copy Number Alterations in Colorectal Cancer Lead to a Differentially Expressed ceRNA Network (ceRNet)
title_sort somatic copy number alterations in colorectal cancer lead to a differentially expressed cerna network cernet
topic colorectal cancer
somatic copy number alterations
long non-coding RNAs
competitive endogenous RNA (ceRNA) network
url https://www.mdpi.com/1467-3045/45/12/597
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