RESUMEN
microRNAs are the post-transcriptional regulators implicated in the initiation and progression of various cancer types, including oral squamous cell carcinoma (OSCC). Here, we investigated the role of miR-377 in OSCC tumorigenesis. miR-377 expression was reduced in OSCC samples and cell line (UPCI-SCC-116), and was associated with patient survival. In vitro restoration of miR-377 repressed cell growth, induced apoptosis, and reduced cell migration. We identified HDAC9 as a target of miR-377 and found miR-377 to regulate HDAC9 and its pro-apoptotic target, NR4A1/Nur77. Our findings show that miR-377 targets HDAC9 pathway in OSCC, suggesting that miR-377-HDAC9 axis may provide a novel therapeutic target for OSCC therapy.
Asunto(s)
Carcinoma de Células Escamosas/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Neoplasias de la Boca/genética , Interferencia de ARN , Regiones no Traducidas 3' , Apoptosis , Secuencia de Bases , Sitios de Unión , Carcinoma de Células Escamosas/enzimología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación hacia Abajo , Represión Enzimática , Histona Desacetilasas , Humanos , Estimación de Kaplan-Meier , MicroARNs/metabolismo , Neoplasias de la Boca/enzimología , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/genética , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/metabolismo , Proteínas RepresorasRESUMEN
BACKGROUND AND AIMS: Postmenopausal osteoporosis (PMO) and type 2 diabetes mellitus (T2DM) frequently coexist in postmenopausal women. The study aimed to explore metabolic variations linked to these circumstances and their simultaneous presence through proton nuclear magnetic resonance metabolomics (1H NMR). MATERIALS AND METHODS: Serum samples from 80 postmenopausal women, including 20 PMO individuals, 20 T2DM, 20 T2DM + PMO, and 20 healthy postmenopausal women, were analyzed using 1H NMR spectroscopy. RESULTS: Our study revealed significant metabolic profile differences among the four groups. Notably, the T2DM + PMO group showed elevated levels of alanine, pyruvate, glutamate, lactate, and aspartate, indicating their involvement in lipid metabolism, energy, and amino acids. Importantly, our multivariate statistical analysis identified a metabolite set that accurately distinguished the groups, suggesting its potential as an early diagnostic marker. CONCLUSION: The 1H NMR metabolomics approach uncovered metabolic biomarkers intricately linked to postmenopausal osteoporosis (PMO), type 2 diabetes mellitus (T2DM), and their concurrent presence. Among these biomarkers, alanine emerged as a pivotal player, showing its significant role in the metabolic landscape associated with PMO and T2DM. These findings shed light on the pathophysiological mechanisms underlying these conditions and underscore alanine's potential as a diagnostic biomarker.