MicroRNA-7 Regulates Migration and Chemoresistance in Non-Hodgkin Lymphoma Cells Through Regulation of KLF4 and YY1
The discovery and description of the role of microRNAs has become very important, specifically due to their participation in the regulation of proteins and transcription factors involved in the development of cancer. microRNA-7 (miR-7) has been described as a negative regulator of several proteins i...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.588893/full |
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| author | Mario Morales-Martinez Mario Morales-Martinez Gabriel G. Vega Gabriel G. Vega Natividad Neri M. J Nambo Isabel Alvarado Ivonne Cuadra M. A. Duran-Padilla Sara Huerta-Yepez Mario I. Vega Mario I. Vega |
| author_facet | Mario Morales-Martinez Mario Morales-Martinez Gabriel G. Vega Gabriel G. Vega Natividad Neri M. J Nambo Isabel Alvarado Ivonne Cuadra M. A. Duran-Padilla Sara Huerta-Yepez Mario I. Vega Mario I. Vega |
| author_sort | Mario Morales-Martinez |
| collection | DOAJ |
| description | The discovery and description of the role of microRNAs has become very important, specifically due to their participation in the regulation of proteins and transcription factors involved in the development of cancer. microRNA-7 (miR-7) has been described as a negative regulator of several proteins involved in cancer, such as YY1 and KLF4. We have recently reported that YY1 and KLF4 play a role in non-Hodgkin lymphoma (NHL) and that the expression of KLF4 is regulated by YY1. Therefore, in this study we analyzed the role of miR-7 in NHL through the negative regulation of YY1 and KLF4. qRT-PCR showed that there is an inverse expression of miR-7 in relation to the expression of YY1 and KLF4 in B-NHL cell lines. The possible regulation of YY1 and KLF4 by miR-7 was analyzed using the constitutive expression or inhibition of miR-7, as well as using reporter plasmids containing the 3 ‘UTR region of YY1 or KLF4. The role of miR-7 in NHL, through the negative regulation of YY1 and KLF4 was determined by chemoresistance and migration assays. We corroborated our results in cell lines, in a TMA from NHL patients including DLBCL and follicular lymphoma subtypes, in where we analyzed miR-7 by ISH and YY1 and KLF4 using IHC. All tumors expressing miR-7 showed a negative correlation with YY1 and KLF4 expression. In addition, expression of miR-7 was analyzed using the GEO Database; miR-7 downregulated expression was associated with pour overall-survival. Our results show for the first time that miR-7 is implicate in the cell migration and chemoresistance in NHL, through the negative regulation of YY1 and KLF4. That also support the evidence that YY1 and KLF4 can be a potential therapeutic target in NHL. |
| first_indexed | 2024-12-11T01:35:41Z |
| format | Article |
| id | doaj.art-05438ea447104fe4ab181ad65a1f052c |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-11T01:35:41Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-05438ea447104fe4ab181ad65a1f052c2022-12-22T01:25:12ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-10-011010.3389/fonc.2020.588893588893MicroRNA-7 Regulates Migration and Chemoresistance in Non-Hodgkin Lymphoma Cells Through Regulation of KLF4 and YY1Mario Morales-Martinez0Mario Morales-Martinez1Gabriel G. Vega2Gabriel G. Vega3Natividad Neri4M. J Nambo5Isabel Alvarado6Ivonne Cuadra7M. A. Duran-Padilla8Sara Huerta-Yepez9Mario I. Vega10Mario I. Vega11Molecular Signal Pathway in Cancer Laboratory, Unidad de Investigación Medica en Enfermedades Oncologicas (UIMEO), Oncology Hospital, Siglo XXI National Medical Center, Instituto Méxicano del Seguro Social (IMSS), Mexico City, MexicoUnidad de Posgrado, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, MexicoMolecular Signal Pathway in Cancer Laboratory, Unidad de Investigación Medica en Enfermedades Oncologicas (UIMEO), Oncology Hospital, Siglo XXI National Medical Center, Instituto Méxicano del Seguro Social (IMSS), Mexico City, MexicoUnidad de Posgrado, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, MexicoDepartment of Hematology, Oncology Hospital, National Medical Center, IMSS, Mexico City, MexicoDepartment of Hematology, Oncology Hospital, National Medical Center, IMSS, Mexico City, MexicoServicio de Anatomía Patológica, Hospital de Oncología, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, MexicoServicio de Anatomía Patológica, Hospital de Oncología, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, MexicoServicio de Patología, Hospital General de México “Eduardo Liceaga”, Facultad de Medicina de la UNAM, Mexico City, MexicoUnidad de Investigación en Enfermedades Oncológicas, Hospital Infantil de México Federico Gómez S.S.A, Mexico City, MexicoMolecular Signal Pathway in Cancer Laboratory, Unidad de Investigación Medica en Enfermedades Oncologicas (UIMEO), Oncology Hospital, Siglo XXI National Medical Center, Instituto Méxicano del Seguro Social (IMSS), Mexico City, MexicoDepartment of Medicine, Hematology-Oncology Division, Greater Los Angeles VA Healthcare Center, UCLA Medical Center, Jonsson Comprehensive Cancer Center, Los Angeles, CA, United StatesThe discovery and description of the role of microRNAs has become very important, specifically due to their participation in the regulation of proteins and transcription factors involved in the development of cancer. microRNA-7 (miR-7) has been described as a negative regulator of several proteins involved in cancer, such as YY1 and KLF4. We have recently reported that YY1 and KLF4 play a role in non-Hodgkin lymphoma (NHL) and that the expression of KLF4 is regulated by YY1. Therefore, in this study we analyzed the role of miR-7 in NHL through the negative regulation of YY1 and KLF4. qRT-PCR showed that there is an inverse expression of miR-7 in relation to the expression of YY1 and KLF4 in B-NHL cell lines. The possible regulation of YY1 and KLF4 by miR-7 was analyzed using the constitutive expression or inhibition of miR-7, as well as using reporter plasmids containing the 3 ‘UTR region of YY1 or KLF4. The role of miR-7 in NHL, through the negative regulation of YY1 and KLF4 was determined by chemoresistance and migration assays. We corroborated our results in cell lines, in a TMA from NHL patients including DLBCL and follicular lymphoma subtypes, in where we analyzed miR-7 by ISH and YY1 and KLF4 using IHC. All tumors expressing miR-7 showed a negative correlation with YY1 and KLF4 expression. In addition, expression of miR-7 was analyzed using the GEO Database; miR-7 downregulated expression was associated with pour overall-survival. Our results show for the first time that miR-7 is implicate in the cell migration and chemoresistance in NHL, through the negative regulation of YY1 and KLF4. That also support the evidence that YY1 and KLF4 can be a potential therapeutic target in NHL.https://www.frontiersin.org/articles/10.3389/fonc.2020.588893/fullmiR-7KLF4YY1hematological malignancesnon-Hodgkin lymphoma |
| spellingShingle | Mario Morales-Martinez Mario Morales-Martinez Gabriel G. Vega Gabriel G. Vega Natividad Neri M. J Nambo Isabel Alvarado Ivonne Cuadra M. A. Duran-Padilla Sara Huerta-Yepez Mario I. Vega Mario I. Vega MicroRNA-7 Regulates Migration and Chemoresistance in Non-Hodgkin Lymphoma Cells Through Regulation of KLF4 and YY1 Frontiers in Oncology miR-7 KLF4 YY1 hematological malignances non-Hodgkin lymphoma |
| title | MicroRNA-7 Regulates Migration and Chemoresistance in Non-Hodgkin Lymphoma Cells Through Regulation of KLF4 and YY1 |
| title_full | MicroRNA-7 Regulates Migration and Chemoresistance in Non-Hodgkin Lymphoma Cells Through Regulation of KLF4 and YY1 |
| title_fullStr | MicroRNA-7 Regulates Migration and Chemoresistance in Non-Hodgkin Lymphoma Cells Through Regulation of KLF4 and YY1 |
| title_full_unstemmed | MicroRNA-7 Regulates Migration and Chemoresistance in Non-Hodgkin Lymphoma Cells Through Regulation of KLF4 and YY1 |
| title_short | MicroRNA-7 Regulates Migration and Chemoresistance in Non-Hodgkin Lymphoma Cells Through Regulation of KLF4 and YY1 |
| title_sort | microrna 7 regulates migration and chemoresistance in non hodgkin lymphoma cells through regulation of klf4 and yy1 |
| topic | miR-7 KLF4 YY1 hematological malignances non-Hodgkin lymphoma |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2020.588893/full |
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