MicroRNA-3666 Suppresses Cell Growth in Head and Neck Squamous Cell Carcinoma Through Inhibition of PFKFB3-Mediated Warburg Effect
Autor: | Yaxuan Cao, Yu Cao, Lan Chen, Bei Wu |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Cell growth Chemistry Glucose uptake medicine.disease Warburg effect Head and neck squamous-cell carcinoma law.invention stomatognathic diseases 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Oncology Apoptosis law 030220 oncology & carcinogenesis microRNA Cancer research medicine Suppressor Pharmacology (medical) Glycolysis |
Zdroj: | OncoTargets and Therapy. 13:9029-9041 |
ISSN: | 1178-6930 |
DOI: | 10.2147/ott.s251992 |
Popis: | Purpose MicroRNA-3666 (miR-3666) is aberrantly expressed and plays critical roles in numerous human tumors. However, the expression pattern, biological role, and mechanisms of action of miR-3666 in head and neck squamous cell carcinoma (HNSCC) remain unknown. Therefore, we attempted to determine the expression status and function of miR-3666 in HNSCC and to explore the underlying mechanisms in detail. Methods In this study, quantitative real-time polymerase chain reaction was carried out to measure the expression of miR-3666 HNSCC tissues. A series of experiments, including a Cell Counting Kit-8 assay, colony formation assay, BrdU incorporation and apoptosis analysis, were applied to test whether miR-3666 affects the growth of HNSCC cells. Glucose uptake and lactate production measurements and extracellular acidification and oxygen consumption rate assays were conducted to determine the effect of miR-3666 on glycolysis. Results We found that miR-3666 showed a decreased expression in HNSCC tissues. Further functional studies demonstrated that miR-3666 inhibited the growth of HNSCC cells by suppressing cell proliferation and promoting apoptosis. Bioinformatics analysis and luciferase reporter assays identified phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3), a key enzyme regulating glycolysis, as a direct target of miR-3666. Through inhibition of PFKFB3, miR-3666 decreased glycolysis in HNSCC cells by reducing the production of F2,6BP. Importantly, glycolysis suppression caused by miR-3666 was found to be required for its inhibitory effect on HNSCC cell growth. Conclusion Our data suggest that miR-3666 functions as a tumor suppressor by decreasing the rate of glycolysis through inhibition of PFKFB3 activity, and this miRNA may present a potential candidate for HNSCC therapy. |
Databáze: | OpenAIRE |
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