Molecular Classification of Colorectal Cancer by microRNA Profiling: Correlation with the Consensus Molecular Subtypes (CMS) and Validation of miR-30b Targets
Colorectal cancer consensus molecular subtypes (CMSs) are widely accepted and constitutes the basis for patient stratification to improve clinical practice. We aimed to find whether miRNAs could reproduce molecular subtypes, and to identify miRNA targets associated to the High-stroma/CMS4 subtype. T...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-10-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/14/21/5175 |
| _version_ | 1797468838620561408 |
|---|---|
| author | Mateo Paz-Cabezas Tania Calvo-López Alejandro Romera-Lopez Daniel Tabas-Madrid Jesus Ogando María-Jesús Fernández-Aceñero Javier Sastre Alberto Pascual-Montano Santos Mañes Eduardo Díaz-Rubio Beatriz Perez-Villamil |
| author_facet | Mateo Paz-Cabezas Tania Calvo-López Alejandro Romera-Lopez Daniel Tabas-Madrid Jesus Ogando María-Jesús Fernández-Aceñero Javier Sastre Alberto Pascual-Montano Santos Mañes Eduardo Díaz-Rubio Beatriz Perez-Villamil |
| author_sort | Mateo Paz-Cabezas |
| collection | DOAJ |
| description | Colorectal cancer consensus molecular subtypes (CMSs) are widely accepted and constitutes the basis for patient stratification to improve clinical practice. We aimed to find whether miRNAs could reproduce molecular subtypes, and to identify miRNA targets associated to the High-stroma/CMS4 subtype. The expression of 939 miRNAs was analyzed in tumors classified in CMS. TALASSO was used to find gene-miRNA interactions. A miR-mRNA regulatory network was constructed using Cytoscape. Candidate gene-miR interactions were validated in 293T cells. Hierarchical-Clustering identified three miRNA tumor subtypes (miR-LS; miR-MI; and miR-HS) which were significantly associated (<i>p</i> < 0.001) to the reported mRNA subtypes. miR-LS correlated with the low-stroma/CMS2; miR-MI with the mucinous-MSI/CMS1 and miR-HS with high-stroma/CMS4. MicroRNA tumor subtypes and association to CMSs were validated with TCGA datasets. TALASSO identified 1462 interactions (<i>p</i> < 0.05) out of 21,615 found between 176 miRs and 788 genes. Based on the regulatory network, 88 miR-mRNA interactions were selected as candidates. This network was functionally validated for the pair miR-30b/SLC6A6. We found that miR-30b overexpression silenced 3′-UTR-SLC6A6-driven luciferase expression in 293T-cells; mutation of the target sequence in the 3′-UTR-SLC6A6 prevented the miR-30b inhibitory effect. In conclusion CRC subtype classification using a miR-signature might facilitate a real-time analysis of the disease course and treatment response. |
| first_indexed | 2024-03-09T19:12:59Z |
| format | Article |
| id | doaj.art-1e34fa5eaf744620adafa4bc94e1a8c8 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T19:12:59Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-1e34fa5eaf744620adafa4bc94e1a8c82023-11-24T04:00:30ZengMDPI AGCancers2072-66942022-10-011421517510.3390/cancers14215175Molecular Classification of Colorectal Cancer by microRNA Profiling: Correlation with the Consensus Molecular Subtypes (CMS) and Validation of miR-30b TargetsMateo Paz-Cabezas0Tania Calvo-López1Alejandro Romera-Lopez2Daniel Tabas-Madrid3Jesus Ogando4María-Jesús Fernández-Aceñero5Javier Sastre6Alberto Pascual-Montano7Santos Mañes8Eduardo Díaz-Rubio9Beatriz Perez-Villamil10Genomics and Microarrays Laboratory, Medical Oncology Department, Instituto de Investigación Sanitaria San Carlos (IdiSSC), Hospital Clinico San Carlos, 28040 Madrid, SpainGenomics and Microarrays Laboratory, Medical Oncology Department, Instituto de Investigación Sanitaria San Carlos (IdiSSC), Hospital Clinico San Carlos, 28040 Madrid, SpainGenomics and Microarrays Laboratory, Medical Oncology Department, Instituto de Investigación Sanitaria San Carlos (IdiSSC), Hospital Clinico San Carlos, 28040 Madrid, SpainImmunology and Oncology Department, Centro Nacional de Biotecnología (CSIC), 28049 Madrid, SpainImmunology and Oncology Department, Centro Nacional de Biotecnología (CSIC), 28049 Madrid, SpainSurgical Pathology, Instituto de Investigación Sanitaria San Carlos (IdiSSC), Hospital Clinico San Carlos, 28040 Madrid, SpainGenomics and Microarrays Laboratory, Medical Oncology Department, Instituto de Investigación Sanitaria San Carlos (IdiSSC), Hospital Clinico San Carlos, 28040 Madrid, SpainImmunology and Oncology Department, Centro Nacional de Biotecnología (CSIC), 28049 Madrid, SpainImmunology and Oncology Department, Centro Nacional de Biotecnología (CSIC), 28049 Madrid, SpainGenomics and Microarrays Laboratory, Medical Oncology Department, Instituto de Investigación Sanitaria San Carlos (IdiSSC), Hospital Clinico San Carlos, 28040 Madrid, SpainGenomics and Microarrays Laboratory, Medical Oncology Department, Instituto de Investigación Sanitaria San Carlos (IdiSSC), Hospital Clinico San Carlos, 28040 Madrid, SpainColorectal cancer consensus molecular subtypes (CMSs) are widely accepted and constitutes the basis for patient stratification to improve clinical practice. We aimed to find whether miRNAs could reproduce molecular subtypes, and to identify miRNA targets associated to the High-stroma/CMS4 subtype. The expression of 939 miRNAs was analyzed in tumors classified in CMS. TALASSO was used to find gene-miRNA interactions. A miR-mRNA regulatory network was constructed using Cytoscape. Candidate gene-miR interactions were validated in 293T cells. Hierarchical-Clustering identified three miRNA tumor subtypes (miR-LS; miR-MI; and miR-HS) which were significantly associated (<i>p</i> < 0.001) to the reported mRNA subtypes. miR-LS correlated with the low-stroma/CMS2; miR-MI with the mucinous-MSI/CMS1 and miR-HS with high-stroma/CMS4. MicroRNA tumor subtypes and association to CMSs were validated with TCGA datasets. TALASSO identified 1462 interactions (<i>p</i> < 0.05) out of 21,615 found between 176 miRs and 788 genes. Based on the regulatory network, 88 miR-mRNA interactions were selected as candidates. This network was functionally validated for the pair miR-30b/SLC6A6. We found that miR-30b overexpression silenced 3′-UTR-SLC6A6-driven luciferase expression in 293T-cells; mutation of the target sequence in the 3′-UTR-SLC6A6 prevented the miR-30b inhibitory effect. In conclusion CRC subtype classification using a miR-signature might facilitate a real-time analysis of the disease course and treatment response.https://www.mdpi.com/2072-6694/14/21/5175colorectal cancermicroRNAsmicroarray gene-expression profilingmolecular classificationprognostic factors |
| spellingShingle | Mateo Paz-Cabezas Tania Calvo-López Alejandro Romera-Lopez Daniel Tabas-Madrid Jesus Ogando María-Jesús Fernández-Aceñero Javier Sastre Alberto Pascual-Montano Santos Mañes Eduardo Díaz-Rubio Beatriz Perez-Villamil Molecular Classification of Colorectal Cancer by microRNA Profiling: Correlation with the Consensus Molecular Subtypes (CMS) and Validation of miR-30b Targets Cancers colorectal cancer microRNAs microarray gene-expression profiling molecular classification prognostic factors |
| title | Molecular Classification of Colorectal Cancer by microRNA Profiling: Correlation with the Consensus Molecular Subtypes (CMS) and Validation of miR-30b Targets |
| title_full | Molecular Classification of Colorectal Cancer by microRNA Profiling: Correlation with the Consensus Molecular Subtypes (CMS) and Validation of miR-30b Targets |
| title_fullStr | Molecular Classification of Colorectal Cancer by microRNA Profiling: Correlation with the Consensus Molecular Subtypes (CMS) and Validation of miR-30b Targets |
| title_full_unstemmed | Molecular Classification of Colorectal Cancer by microRNA Profiling: Correlation with the Consensus Molecular Subtypes (CMS) and Validation of miR-30b Targets |
| title_short | Molecular Classification of Colorectal Cancer by microRNA Profiling: Correlation with the Consensus Molecular Subtypes (CMS) and Validation of miR-30b Targets |
| title_sort | molecular classification of colorectal cancer by microrna profiling correlation with the consensus molecular subtypes cms and validation of mir 30b targets |
| topic | colorectal cancer microRNAs microarray gene-expression profiling molecular classification prognostic factors |
| url | https://www.mdpi.com/2072-6694/14/21/5175 |
| work_keys_str_mv | AT mateopazcabezas molecularclassificationofcolorectalcancerbymicrornaprofilingcorrelationwiththeconsensusmolecularsubtypescmsandvalidationofmir30btargets AT taniacalvolopez molecularclassificationofcolorectalcancerbymicrornaprofilingcorrelationwiththeconsensusmolecularsubtypescmsandvalidationofmir30btargets AT alejandroromeralopez molecularclassificationofcolorectalcancerbymicrornaprofilingcorrelationwiththeconsensusmolecularsubtypescmsandvalidationofmir30btargets AT danieltabasmadrid molecularclassificationofcolorectalcancerbymicrornaprofilingcorrelationwiththeconsensusmolecularsubtypescmsandvalidationofmir30btargets AT jesusogando molecularclassificationofcolorectalcancerbymicrornaprofilingcorrelationwiththeconsensusmolecularsubtypescmsandvalidationofmir30btargets AT mariajesusfernandezacenero molecularclassificationofcolorectalcancerbymicrornaprofilingcorrelationwiththeconsensusmolecularsubtypescmsandvalidationofmir30btargets AT javiersastre molecularclassificationofcolorectalcancerbymicrornaprofilingcorrelationwiththeconsensusmolecularsubtypescmsandvalidationofmir30btargets AT albertopascualmontano molecularclassificationofcolorectalcancerbymicrornaprofilingcorrelationwiththeconsensusmolecularsubtypescmsandvalidationofmir30btargets AT santosmanes molecularclassificationofcolorectalcancerbymicrornaprofilingcorrelationwiththeconsensusmolecularsubtypescmsandvalidationofmir30btargets AT eduardodiazrubio molecularclassificationofcolorectalcancerbymicrornaprofilingcorrelationwiththeconsensusmolecularsubtypescmsandvalidationofmir30btargets AT beatrizperezvillamil molecularclassificationofcolorectalcancerbymicrornaprofilingcorrelationwiththeconsensusmolecularsubtypescmsandvalidationofmir30btargets |