Metastatic breast tumors downregulate miR-145 regulating the hypoxia-induced vasculogenic mimicry
Tumor cells grow in three-dimensional (3D) channels-like structures denoted as vasculogenic mimicry (VM), which provides a route for nutrients and oxygen acquisition. VM is activated by hypoxia and associated with metastasis and poor prognosis. MetastamiRs are microRNAs regulating metastasis, howeve...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523323000669 |
| _version_ | 1797823388677308416 |
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| author | Estefania Contreras-Sanzón Ángeles Carlos-Reyes Mónica Sierra-Martínez Gustavo Acosta-Altamirano Cesar Luna-Rivero David Núñez-Corona Alejandra Paola García-Hernández Eloisa Ibarra-Sierra Horacio Vidrio-Morgado María Elizbeth Alvarez-Sánchez Laurence A. Marchat César López-Camarillo |
| author_facet | Estefania Contreras-Sanzón Ángeles Carlos-Reyes Mónica Sierra-Martínez Gustavo Acosta-Altamirano Cesar Luna-Rivero David Núñez-Corona Alejandra Paola García-Hernández Eloisa Ibarra-Sierra Horacio Vidrio-Morgado María Elizbeth Alvarez-Sánchez Laurence A. Marchat César López-Camarillo |
| author_sort | Estefania Contreras-Sanzón |
| collection | DOAJ |
| description | Tumor cells grow in three-dimensional (3D) channels-like structures denoted as vasculogenic mimicry (VM), which provides a route for nutrients and oxygen acquisition. VM is activated by hypoxia and associated with metastasis and poor prognosis. MetastamiRs are microRNAs regulating metastasis, however, if they control VM in breast cancer remains poorly understood. The aim of this study was to evaluate the expression of VM-associated microRNAs in tumors of metastatic breast cancer patients. Firstly, we constructed microRNAs/mRNAs coregulation networks using expression data from TCGA databases. Dozens of microRNAs regulating genes involved in VM and metastasis were found. Of these, we selected 10 microRNAs for further characterization. The presence of VM in histological samples from patients with or without metastasis was evaluated using CD31-/PAS+ immunophenotyping. Remarkably, data showed that VM was significantly increased in tumors from patients with metastasis in comparison with no-metastatic group. Gene expression analysis indicated that miR-145, miR-142-3p, miR-31, miR-148a, miR-200b-3p and miR-526b were downregulated in primary tumors from patients with metastatic disease and positive for VM. Moreover, modulated microRNAs showed a predictive clinical value in overall survival in a cohort (n=1262) of breast cancer patients. Of these, we evaluated the role of miR-145 in formation of hypoxia-induced 3D channels-like using an in vitro model that recapitulates the early stages of VM. Data showed that miR-145 mimics was able to abolish the VM development in both metastatic Hs578t and MDA-MB-231 breast cancer cells. In conclusion, manipulation of miR-145 levels may represent a therapeutic approach in metastatic breast cancer patients that developed VM. |
| first_indexed | 2024-03-13T10:23:17Z |
| format | Article |
| id | doaj.art-e9183bdb80fa452ba37d3259d269d580 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-03-13T10:23:17Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-e9183bdb80fa452ba37d3259d269d5802023-05-20T04:29:47ZengElsevierTranslational Oncology1936-52332023-07-0133101680Metastatic breast tumors downregulate miR-145 regulating the hypoxia-induced vasculogenic mimicryEstefania Contreras-Sanzón0Ángeles Carlos-Reyes1Mónica Sierra-Martínez2Gustavo Acosta-Altamirano3Cesar Luna-Rivero4David Núñez-Corona5Alejandra Paola García-Hernández6Eloisa Ibarra-Sierra7Horacio Vidrio-Morgado8María Elizbeth Alvarez-Sánchez9Laurence A. Marchat10César López-Camarillo11Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, CDMX, MéxicoLaboratorio de Onco-inmunobiologia, Instituto Nacional de Enfermedades Respiratorias ''Ismael Cosío Villegas'', CDMX, Mexico.Unidad de Investigación en Salud del Hospital Regional de Alta Especialidad de Ixtapaluca, Estado de Mexico, Mexico.Dirección de Planeación, Enseñanza e Investigación del Hospital Regional de Alta Especialidad de Ixtapaluca, Estado de Mexico, Mexico.Servicio de Patología, Instituto Nacional de Enfermedades Respiratorias ''Ismael Cosío Villegas'', CDMX, Mexico.Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, CDMX, MéxicoPosgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, CDMX, MéxicoDepartamento de Investigacion. Instituto Estatal de Cancerologia “Dr. Arturo Béltran Ortega”, Acapulco, Guerrero, Mexico.Departamento de Investigacion. Instituto Estatal de Cancerologia “Dr. Arturo Béltran Ortega”, Acapulco, Guerrero, Mexico.Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, CDMX, MéxicoLaboratorio de Biomedicina Molecular II, Programa en Biomedicina Molecular y Red de Biotecnologia, Instituto Politecnico Nacional, CDMX, MexicoPosgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, CDMX, México; Corresponding author: César López-Camarillo. Universidad Autónoma de la Ciudad de México, San Lorenzo 290. Col. Del Valle. 03100, CDMX, MéxicoTumor cells grow in three-dimensional (3D) channels-like structures denoted as vasculogenic mimicry (VM), which provides a route for nutrients and oxygen acquisition. VM is activated by hypoxia and associated with metastasis and poor prognosis. MetastamiRs are microRNAs regulating metastasis, however, if they control VM in breast cancer remains poorly understood. The aim of this study was to evaluate the expression of VM-associated microRNAs in tumors of metastatic breast cancer patients. Firstly, we constructed microRNAs/mRNAs coregulation networks using expression data from TCGA databases. Dozens of microRNAs regulating genes involved in VM and metastasis were found. Of these, we selected 10 microRNAs for further characterization. The presence of VM in histological samples from patients with or without metastasis was evaluated using CD31-/PAS+ immunophenotyping. Remarkably, data showed that VM was significantly increased in tumors from patients with metastasis in comparison with no-metastatic group. Gene expression analysis indicated that miR-145, miR-142-3p, miR-31, miR-148a, miR-200b-3p and miR-526b were downregulated in primary tumors from patients with metastatic disease and positive for VM. Moreover, modulated microRNAs showed a predictive clinical value in overall survival in a cohort (n=1262) of breast cancer patients. Of these, we evaluated the role of miR-145 in formation of hypoxia-induced 3D channels-like using an in vitro model that recapitulates the early stages of VM. Data showed that miR-145 mimics was able to abolish the VM development in both metastatic Hs578t and MDA-MB-231 breast cancer cells. In conclusion, manipulation of miR-145 levels may represent a therapeutic approach in metastatic breast cancer patients that developed VM.http://www.sciencedirect.com/science/article/pii/S1936523323000669breast cancervasculogenic mimicrymetastasismiR-145therapy |
| spellingShingle | Estefania Contreras-Sanzón Ángeles Carlos-Reyes Mónica Sierra-Martínez Gustavo Acosta-Altamirano Cesar Luna-Rivero David Núñez-Corona Alejandra Paola García-Hernández Eloisa Ibarra-Sierra Horacio Vidrio-Morgado María Elizbeth Alvarez-Sánchez Laurence A. Marchat César López-Camarillo Metastatic breast tumors downregulate miR-145 regulating the hypoxia-induced vasculogenic mimicry Translational Oncology breast cancer vasculogenic mimicry metastasis miR-145 therapy |
| title | Metastatic breast tumors downregulate miR-145 regulating the hypoxia-induced vasculogenic mimicry |
| title_full | Metastatic breast tumors downregulate miR-145 regulating the hypoxia-induced vasculogenic mimicry |
| title_fullStr | Metastatic breast tumors downregulate miR-145 regulating the hypoxia-induced vasculogenic mimicry |
| title_full_unstemmed | Metastatic breast tumors downregulate miR-145 regulating the hypoxia-induced vasculogenic mimicry |
| title_short | Metastatic breast tumors downregulate miR-145 regulating the hypoxia-induced vasculogenic mimicry |
| title_sort | metastatic breast tumors downregulate mir 145 regulating the hypoxia induced vasculogenic mimicry |
| topic | breast cancer vasculogenic mimicry metastasis miR-145 therapy |
| url | http://www.sciencedirect.com/science/article/pii/S1936523323000669 |
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