دورية أكاديمية
أعرض في EDS

Negative Regulation of Serine Threonine Kinase 11 (STK11) through miR-100 in Head and Neck Cancer.

التفاصيل البيبلوغرافية
العنوان: Negative Regulation of Serine Threonine Kinase 11 (STK11) through miR-100 in Head and Neck Cancer.
المؤلفون: Figueroa-González G; Unidad Multidisciplinaria de Investigación Experimental Zaragoza (UMIEZ), Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Mexico City 09230, Mexico.; Unidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, Mexico., Carrillo-Hernández JF; Unidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, Mexico., Perez-Rodriguez I; Unidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, Mexico., Cantú de León D; Unidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, Mexico., Campos-Parra AD; Unidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, Mexico., Martínez-Gutiérrez AD; Unidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, Mexico., Coronel-Hernández J; Unidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, Mexico., García-Castillo V; Unidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica del Cáncer, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Edo.Mex, Mexico., López-Camarillo C; Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Mexico City 09790, Mexico., Peralta-Zaragoza O; Dirección de Infecciones Crónicas y Cáncer, Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca 62100, Morelos, Mexico., Jacobo-Herrera NJ; Unidad de Bioquímica, Instituto Nacional de Nutrición y Ciencias Médicas, Salvador Zubirán, Mexico City 14000, Mexico., Guardado-Estrada M; Laboratorio de Genética, Licenciatura en Ciencia Forense, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04360, Mexico., Pérez-Plasencia C; Unidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica, Instituto Nacional de Cancerología, Mexico City 14080, Mexico.; Unidad de Investigación Biomédica en Cáncer, Laboratorio de Genómica del Cáncer, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Edo.Mex, Mexico.
المصدر: Genes [Genes (Basel)] 2020 Sep 08; Vol. 11 (9). Date of Electronic Publication: 2020 Sep 08.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101551097 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4425 (Electronic) Linking ISSN: 20734425 NLM ISO Abbreviation: Genes (Basel) Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel : MDPI
مواضيع طبية MeSH: Gene Expression Regulation, Neoplastic*, Biomarkers, Tumor/*metabolism , Head and Neck Neoplasms/*pathology , MicroRNAs/*genetics , Protein Serine-Threonine Kinases/*metabolism , Squamous Cell Carcinoma of Head and Neck/*pathology, AMP-Activated Protein Kinase Kinases ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Cell Movement ; Cell Proliferation ; Female ; Head and Neck Neoplasms/genetics ; Head and Neck Neoplasms/metabolism ; Humans ; Male ; Middle Aged ; Prognosis ; Protein Serine-Threonine Kinases/genetics ; Squamous Cell Carcinoma of Head and Neck/genetics ; Squamous Cell Carcinoma of Head and Neck/metabolism ; Survival Rate ; Tumor Cells, Cultured
مستخلص: 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.
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فهرسة مساهمة: Keywords: STK11; head and neck cancer; microRNA; mir-100; promoter methylation
المشرفين على المادة: 0 (Biomarkers, Tumor)
0 (MIRN100 microRNA, human)
0 (MicroRNAs)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
EC 2.7.11.1 (STK11 protein, human)
EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)
تواريخ الأحداث: Date Created: 20200911 Date Completed: 20210331 Latest Revision: 20231104
رمز التحديث: 20231104
مُعرف محوري في PubMed: PMC7563199
DOI: 10.3390/genes11091058
PMID: 32911741
قاعدة البيانات: MEDLINE
الوصف
تدمد:2073-4425
DOI:10.3390/genes11091058