Negative Regulation of Serine Threonine Kinase 11 (STK11) through miR-100 in Head and Neck Cancer
Background: Serine Threonine Kinase 11 (STK11), also known as LKB1, is a tumor suppressor gene that regulates several biological processes such as apoptosis, energetic metabolism, proliferation, invasion, and migration. During malignant progression, different types of cancer inhibit STK11 function b...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-09-01
|
| Series: | Genes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4425/11/9/1058 |
| _version_ | 1797554310529155072 |
|---|---|
| author | Gabriela Figueroa-González José F. Carrillo-Hernández Itzel Perez-Rodriguez David Cantú de León Alma D. Campos-Parra Antonio D. Martínez-Gutiérrez Jossimar Coronel-Hernández Verónica García-Castillo César López-Camarillo Oscar Peralta-Zaragoza Nadia J. Jacobo-Herrera Mariano Guardado-Estrada Carlos Pérez-Plasencia |
| author_facet | Gabriela Figueroa-González José F. Carrillo-Hernández Itzel Perez-Rodriguez David Cantú de León Alma D. Campos-Parra Antonio D. Martínez-Gutiérrez Jossimar Coronel-Hernández Verónica García-Castillo César López-Camarillo Oscar Peralta-Zaragoza Nadia J. Jacobo-Herrera Mariano Guardado-Estrada Carlos Pérez-Plasencia |
| author_sort | Gabriela Figueroa-González |
| collection | DOAJ |
| description | Background: Serine Threonine Kinase 11 (STK11), also known as LKB1, is a tumor suppressor gene that regulates several biological processes such as apoptosis, energetic metabolism, proliferation, invasion, and migration. During malignant progression, different types of cancer inhibit STK11 function by mutation or epigenetic inactivation. In Head and Neck Cancer, it is unclear what mechanism is involved in decreasing STK11 levels. Thus, the present work aims to determine whether STK11 expression might be regulated through epigenetic or post-translational mechanisms. Methods: Expression levels and methylation status for STK11 were analyzed in 59 cases of head and neck cancer and 10 healthy tissue counterparts. Afterward, we sought to identify candidate miRNAs exerting post-transcriptional regulation of STK11. Then, we assessed a luciferase gene reporter assay to know if miRNAs directly target STK11 mRNA. The expression levels of the clinical significance of mir-100-3p, -5p, and STK11 in 495 HNC specimens obtained from the TCGA database were further analyzed. Finally, the Kaplan–Meier method was used to estimate the prognostic significance of the miRNAs for Overall Survival, and survival curves were compared through the log-rank test. Results: STK11 was under-expressed, and its promoter region was demethylated or partially methylated. miR-17-5p, miR-106a-5p, miR-100-3p, and miR-100-5p could be negative regulators of STK11. Our experimental data suggested evidence that miR-100-3p and -5p were over-expressed in analyzed tumor patient samples. Luciferase gene reporter assay experiments showed that miR-100-3p targets and down-regulates STK11 mRNA directly. With respect to overall survival, STK11 expression level was significant for predicting clinical outcomes. Conclusion: This is, to our knowledge, the first report of miR-100-3p targeting STK11 in HNC. Together, these findings may support the importance of regulation of STK11 through post-transcriptional regulation in HNC and the possible contribution to the carcinogenesis process in this neoplasia. |
| first_indexed | 2024-03-10T16:30:10Z |
| format | Article |
| id | doaj.art-ed021642503d45cda37ff000bf1cc2f2 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T16:30:10Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-ed021642503d45cda37ff000bf1cc2f22023-11-20T12:57:57ZengMDPI AGGenes2073-44252020-09-01119105810.3390/genes11091058Negative Regulation of Serine Threonine Kinase 11 (STK11) through miR-100 in Head and Neck CancerGabriela Figueroa-González0José F. Carrillo-Hernández1Itzel Perez-Rodriguez2David Cantú de León3Alma D. Campos-Parra4Antonio D. Martínez-Gutiérrez5Jossimar Coronel-Hernández6Verónica García-Castillo7César López-Camarillo8Oscar Peralta-Zaragoza9Nadia J. Jacobo-Herrera10Mariano Guardado-Estrada11Carlos Pérez-Plasencia12Unidad Multidisciplinaria de Investigación Experimental Zaragoza (UMIEZ), Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Mexico City 09230, MexicoUnidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, MexicoUnidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, MexicoUnidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, MexicoUnidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, MexicoUnidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, MexicoUnidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, MexicoUnidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica del Cáncer, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Edo.Mex, MexicoPosgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Mexico City 09790, MexicoDirección de Infecciones Crónicas y Cáncer, Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca 62100, Morelos, MexicoUnidad de Bioquímica, Instituto Nacional de Nutrición y Ciencias Médicas, Salvador Zubirán, Mexico City 14000, MexicoLaboratorio de Genética, Licenciatura en Ciencia Forense, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04360, MexicoUnidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, MexicoBackground: Serine Threonine Kinase 11 (STK11), also known as LKB1, is a tumor suppressor gene that regulates several biological processes such as apoptosis, energetic metabolism, proliferation, invasion, and migration. During malignant progression, different types of cancer inhibit STK11 function by mutation or epigenetic inactivation. In Head and Neck Cancer, it is unclear what mechanism is involved in decreasing STK11 levels. Thus, the present work aims to determine whether STK11 expression might be regulated through epigenetic or post-translational mechanisms. Methods: Expression levels and methylation status for STK11 were analyzed in 59 cases of head and neck cancer and 10 healthy tissue counterparts. Afterward, we sought to identify candidate miRNAs exerting post-transcriptional regulation of STK11. Then, we assessed a luciferase gene reporter assay to know if miRNAs directly target STK11 mRNA. The expression levels of the clinical significance of mir-100-3p, -5p, and STK11 in 495 HNC specimens obtained from the TCGA database were further analyzed. Finally, the Kaplan–Meier method was used to estimate the prognostic significance of the miRNAs for Overall Survival, and survival curves were compared through the log-rank test. Results: STK11 was under-expressed, and its promoter region was demethylated or partially methylated. miR-17-5p, miR-106a-5p, miR-100-3p, and miR-100-5p could be negative regulators of STK11. Our experimental data suggested evidence that miR-100-3p and -5p were over-expressed in analyzed tumor patient samples. Luciferase gene reporter assay experiments showed that miR-100-3p targets and down-regulates STK11 mRNA directly. With respect to overall survival, STK11 expression level was significant for predicting clinical outcomes. Conclusion: This is, to our knowledge, the first report of miR-100-3p targeting STK11 in HNC. Together, these findings may support the importance of regulation of STK11 through post-transcriptional regulation in HNC and the possible contribution to the carcinogenesis process in this neoplasia.https://www.mdpi.com/2073-4425/11/9/1058microRNAmir-100<i>STK11</i>promoter methylationhead and neck cancer |
| spellingShingle | Gabriela Figueroa-González José F. Carrillo-Hernández Itzel Perez-Rodriguez David Cantú de León Alma D. Campos-Parra Antonio D. Martínez-Gutiérrez Jossimar Coronel-Hernández Verónica García-Castillo César López-Camarillo Oscar Peralta-Zaragoza Nadia J. Jacobo-Herrera Mariano Guardado-Estrada Carlos Pérez-Plasencia Negative Regulation of Serine Threonine Kinase 11 (STK11) through miR-100 in Head and Neck Cancer Genes microRNA mir-100 <i>STK11</i> promoter methylation head and neck cancer |
| title | Negative Regulation of Serine Threonine Kinase 11 (STK11) through miR-100 in Head and Neck Cancer |
| title_full | Negative Regulation of Serine Threonine Kinase 11 (STK11) through miR-100 in Head and Neck Cancer |
| title_fullStr | Negative Regulation of Serine Threonine Kinase 11 (STK11) through miR-100 in Head and Neck Cancer |
| title_full_unstemmed | Negative Regulation of Serine Threonine Kinase 11 (STK11) through miR-100 in Head and Neck Cancer |
| title_short | Negative Regulation of Serine Threonine Kinase 11 (STK11) through miR-100 in Head and Neck Cancer |
| title_sort | negative regulation of serine threonine kinase 11 stk11 through mir 100 in head and neck cancer |
| topic | microRNA mir-100 <i>STK11</i> promoter methylation head and neck cancer |
| url | https://www.mdpi.com/2073-4425/11/9/1058 |
| work_keys_str_mv | AT gabrielafigueroagonzalez negativeregulationofserinethreoninekinase11stk11throughmir100inheadandneckcancer AT josefcarrillohernandez negativeregulationofserinethreoninekinase11stk11throughmir100inheadandneckcancer AT itzelperezrodriguez negativeregulationofserinethreoninekinase11stk11throughmir100inheadandneckcancer AT davidcantudeleon negativeregulationofserinethreoninekinase11stk11throughmir100inheadandneckcancer AT almadcamposparra negativeregulationofserinethreoninekinase11stk11throughmir100inheadandneckcancer AT antoniodmartinezgutierrez negativeregulationofserinethreoninekinase11stk11throughmir100inheadandneckcancer AT jossimarcoronelhernandez negativeregulationofserinethreoninekinase11stk11throughmir100inheadandneckcancer AT veronicagarciacastillo negativeregulationofserinethreoninekinase11stk11throughmir100inheadandneckcancer AT cesarlopezcamarillo negativeregulationofserinethreoninekinase11stk11throughmir100inheadandneckcancer AT oscarperaltazaragoza negativeregulationofserinethreoninekinase11stk11throughmir100inheadandneckcancer AT nadiajjacoboherrera negativeregulationofserinethreoninekinase11stk11throughmir100inheadandneckcancer AT marianoguardadoestrada negativeregulationofserinethreoninekinase11stk11throughmir100inheadandneckcancer AT carlosperezplasencia negativeregulationofserinethreoninekinase11stk11throughmir100inheadandneckcancer |