rs12416605:C>T in MIR938 associates with gastric cancer through affecting the regulation of the CXCL12 chemokine gene
Abstract Background MicroRNAs are small regulatory RNAs with important roles in carcinogenesis. Genetic variants in these regulatory molecules may contribute to disease. We aim to identify allelic variants in microRNAs as susceptibility factors to gastric cancer using association studies and functio...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-08-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.832 |
| _version_ | 1798016729828294656 |
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| author | Ignasi Torruella‐Loran María Karla Ramirez Viña Daniela Zapata‐Contreras Xavier Muñoz Eva Garcia‐Ramallo Catalina Bonet Carlos A. Gonzalez Núria Sala Yolanda Espinosa‐Parrilla on behalf of the EPIC gastric cancer working group |
| author_facet | Ignasi Torruella‐Loran María Karla Ramirez Viña Daniela Zapata‐Contreras Xavier Muñoz Eva Garcia‐Ramallo Catalina Bonet Carlos A. Gonzalez Núria Sala Yolanda Espinosa‐Parrilla on behalf of the EPIC gastric cancer working group |
| author_sort | Ignasi Torruella‐Loran |
| collection | DOAJ |
| description | Abstract Background MicroRNAs are small regulatory RNAs with important roles in carcinogenesis. Genetic variants in these regulatory molecules may contribute to disease. We aim to identify allelic variants in microRNAs as susceptibility factors to gastric cancer using association studies and functional approaches. Methods Twenty‐one single nucleotide variants potentially functional, because of their location in either the seed, mature or precursor region of 22 microRNAs, were selected for association studies. Genetic association with gastric cancer in 365 cases and 1,284 matched controls (European Prospective Investigation into Cancer and Nutrition Cohort) was analysed using logistic regression. MicroRNA overexpression, transcriptome analysis, and target gene validation experiments were performed for functional studies. Results rs3746444:T>C, in the seed of MIR499A and mature MIR499B, associated with the cardia adenocarcinoma location; rs12416605:C>T, in the seed of MIR938, associated with the diffuse subtype; and rs2114358:T>C, in the precursor MIR1206, associated with the noncardia phenotype. In all cases, the association was inverse, indicating a protective affect against gastric cancer of the three minor allelic variants. MIR499 rs3746444:T>C and MIR1206 rs2114358:T>C are reported to affect the expression of these miRNAs, but the effect of MIR938 rs12416605:C>T is unknown yet. Functional approaches showed that the expression of MIR938 is affected by rs12416605:C>T and revealed that MIR938 could regulate a subset of cancer‐related genes in an allele‐specific fashion. Furthermore, we demonstrated that CXCL12, a chemokine participating in gastric cancer metastasis, is specifically regulated by only one of the rs12416605:C>T alleles. Conclusion rs12416605 appears to be involved in gastric cancer by affecting the regulatory function of MIR938 on genes related to this cancer type, particularly on CXCL12 posttranscriptional regulation. |
| first_indexed | 2024-04-11T15:55:26Z |
| format | Article |
| id | doaj.art-2867f72999454974818c0d4fc1f9dc8a |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-11T15:55:26Z |
| publishDate | 2019-08-01 |
| publisher | Wiley |
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| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-2867f72999454974818c0d4fc1f9dc8a2022-12-22T04:15:11ZengWileyMolecular Genetics & Genomic Medicine2324-92692019-08-0178n/an/a10.1002/mgg3.832rs12416605:C>T in MIR938 associates with gastric cancer through affecting the regulation of the CXCL12 chemokine geneIgnasi Torruella‐Loran0María Karla Ramirez Viña1Daniela Zapata‐Contreras2Xavier Muñoz3Eva Garcia‐Ramallo4Catalina Bonet5Carlos A. Gonzalez6Núria Sala7Yolanda Espinosa‐Parrilla8on behalf of the EPIC gastric cancer working groupDepartment of Experimental and Health Sciences IBE, Institute of Evolutionary Biology (Universitat Pompeu Fabra‐CSIC) Barcelona SpainSchool of Medicine Universidad de Magallanes Punta Arenas ChileSchool of Medicine Universidad de Magallanes Punta Arenas ChileMolecular Epidemiology Group, Translational Research Laboratory Catalan Institute of Oncology‐IDIBELL Barcelona SpainDepartment of Experimental and Health Sciences IBE, Institute of Evolutionary Biology (Universitat Pompeu Fabra‐CSIC) Barcelona SpainUnit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program Catalan Institute of Oncology‐Bellvitge Biomedical Research Institute (ICO‐IDIBELL) Barcelona SpainUnit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program Catalan Institute of Oncology‐Bellvitge Biomedical Research Institute (ICO‐IDIBELL) Barcelona SpainMolecular Epidemiology Group, Translational Research Laboratory Catalan Institute of Oncology‐IDIBELL Barcelona SpainDepartment of Experimental and Health Sciences IBE, Institute of Evolutionary Biology (Universitat Pompeu Fabra‐CSIC) Barcelona SpainAbstract Background MicroRNAs are small regulatory RNAs with important roles in carcinogenesis. Genetic variants in these regulatory molecules may contribute to disease. We aim to identify allelic variants in microRNAs as susceptibility factors to gastric cancer using association studies and functional approaches. Methods Twenty‐one single nucleotide variants potentially functional, because of their location in either the seed, mature or precursor region of 22 microRNAs, were selected for association studies. Genetic association with gastric cancer in 365 cases and 1,284 matched controls (European Prospective Investigation into Cancer and Nutrition Cohort) was analysed using logistic regression. MicroRNA overexpression, transcriptome analysis, and target gene validation experiments were performed for functional studies. Results rs3746444:T>C, in the seed of MIR499A and mature MIR499B, associated with the cardia adenocarcinoma location; rs12416605:C>T, in the seed of MIR938, associated with the diffuse subtype; and rs2114358:T>C, in the precursor MIR1206, associated with the noncardia phenotype. In all cases, the association was inverse, indicating a protective affect against gastric cancer of the three minor allelic variants. MIR499 rs3746444:T>C and MIR1206 rs2114358:T>C are reported to affect the expression of these miRNAs, but the effect of MIR938 rs12416605:C>T is unknown yet. Functional approaches showed that the expression of MIR938 is affected by rs12416605:C>T and revealed that MIR938 could regulate a subset of cancer‐related genes in an allele‐specific fashion. Furthermore, we demonstrated that CXCL12, a chemokine participating in gastric cancer metastasis, is specifically regulated by only one of the rs12416605:C>T alleles. Conclusion rs12416605 appears to be involved in gastric cancer by affecting the regulatory function of MIR938 on genes related to this cancer type, particularly on CXCL12 posttranscriptional regulation.https://doi.org/10.1002/mgg3.832functional SNVgastric cancergene regulationgenetic susceptibilitymicroRNA |
| spellingShingle | Ignasi Torruella‐Loran María Karla Ramirez Viña Daniela Zapata‐Contreras Xavier Muñoz Eva Garcia‐Ramallo Catalina Bonet Carlos A. Gonzalez Núria Sala Yolanda Espinosa‐Parrilla on behalf of the EPIC gastric cancer working group rs12416605:C>T in MIR938 associates with gastric cancer through affecting the regulation of the CXCL12 chemokine gene Molecular Genetics & Genomic Medicine functional SNV gastric cancer gene regulation genetic susceptibility microRNA |
| title | rs12416605:C>T in MIR938 associates with gastric cancer through affecting the regulation of the CXCL12 chemokine gene |
| title_full | rs12416605:C>T in MIR938 associates with gastric cancer through affecting the regulation of the CXCL12 chemokine gene |
| title_fullStr | rs12416605:C>T in MIR938 associates with gastric cancer through affecting the regulation of the CXCL12 chemokine gene |
| title_full_unstemmed | rs12416605:C>T in MIR938 associates with gastric cancer through affecting the regulation of the CXCL12 chemokine gene |
| title_short | rs12416605:C>T in MIR938 associates with gastric cancer through affecting the regulation of the CXCL12 chemokine gene |
| title_sort | rs12416605 c t in mir938 associates with gastric cancer through affecting the regulation of the cxcl12 chemokine gene |
| topic | functional SNV gastric cancer gene regulation genetic susceptibility microRNA |
| url | https://doi.org/10.1002/mgg3.832 |
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