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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MDPI AG
2023-11-01
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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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issn | 1467-3037 1467-3045 |
language | English |
last_indexed | 2024-03-08T20:53:58Z |
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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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