Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Laryngeal squamous cell carcinoma (LSCC) is the most common form of laryngeal carcinoma with poor prognosis. Exploring novel factors involved in the progression of LSCC is quite necessary for understanding the mechanisms and designing therapeutic strategies for LSCC. In this study, we showed that miR-125b-5p was significantly down-regulated in LSCC tissues and cell lines. The decreased expression of miR-125b-5p was associated with the tumor differentiation, metastasis and high clinical stage of the LSCC patients. Overexpression of miR-125b-5p suppressed the proliferation and induced apoptosis of LSCC cells. Bioinformatics analysis predicted hexokinase-2 (HK2), an essential enzyme involved in the glycolysis of cancer cells, as one of the downstream targets of miR-125b-5p. Further molecular studies showed that highly expressed miR-125b-5p bound the 3'-UTR of HK2 and decreased both the mRNA and protein levels of HK2. Consistent with the function of HK2 in glycolytic metabolism, overexpression of miR-125b-5p significantly suppressed the glucose consumption and lactate production of LSCC cells. Notably, restoration the expression of HK2 attenuated the inhibitory effect of miR-125b-5p on the glycolysis of LSCC cells. The inverse correlation between the expression of miR-125b-5p and HK2 in LSCC tissues further supported the involvement of miR-125b-5p-HK2 axis in the progression of LSCC. Collectively, these finding suggested the miR-125b-5p-HK2 pathway as a novel mechanism in regulating the glycolysis and progression of LSCC.
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PMID:MiR-125b-5p suppressed the glycolysis of laryngeal squamous cell carcinoma by down-regulating hexokinase-2. 2986 98

The clinical management of head and neck squamous cell carcinoma (HNSCC) commonly involves chemoradiotherapy, but recurrences often occur that are associated with radioresistance. Using human SQD9 laryngeal squamous cell carcinoma cancer cells as a model, we aimed to identify metabolic changes associated with acquired radioresistance. In a top-down approach, matched radiosensitive and radioresistant SQD9 cells were generated and metabolically compared, focusing on glycolysis, oxidative phosphorylation (OXPHOS) and ROS production. The cell cycle, clonogenicity, tumor growth in mice and DNA damage-repair were assessed. Mitochondrial DNA (mtDNA) was sequenced. In a bottom-up approach, matched glycolytic and oxidative SQD9 cells were generated using FACS-sorting, and tested for their radiosensitivity/radioresistance. We found that acquired radioresistance is associated with a shift from a glycolytic to a more oxidative metabolism in SQD9 cells. The opposite was also true, as the most oxidative fraction isolated from SQD9 wild-type cells was also more radioresistant than the most glycolytic fraction. However, neither reduced hexokinase expression nor OXPHOS were directly responsible for the radioresistant phenotype. Radiosensitive and radioresistant cells had similar proliferation rates and were equally efficient for ATP production. They were equally sensitive to redox stress and had similar DNA damage repair, but radioresistant cells had an increased number of mitochondria and a higher mtDNA content. Thus, an oxidative switch is associated with but is not responsible for acquired radioresistance in human SQD9 cells. In radioresistant cells, more abundant and fitter mitochondria could help to preserve mitochondrial functions upon irradiation.
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PMID:Fitter Mitochondria Are Associated With Radioresistance in Human Head and Neck SQD9 Cancer Cells. 3223 67