ABSTRACT
As an important component of the tumor microenvironment, cancer-associated fibroblasts (CAFs) secrete energy metabolites to supply energy for tumor progression. Abnormal regulation of long noncoding RNAs (lncRNAs) is thought to contribute to glucose metabolism, but the role of lncRNAs in glycolysis in oral CAFs has not been systematically examined. In the present study, by using RNA sequencing and bioinformatics analysis, we analyzed the lncRNA/mRNA profiles of normal fibroblasts (NFs) derived from normal tissues and CAFs derived from patients with oral squamous cell carcinoma (OSCC). LncRNA H19 was identified as a key lncRNA in oral CAFs and was synchronously upregulated in both oral cancer cell lines and CAFs. Using small interfering RNA (siRNA) strategies, we determined that lncRNA H19 knockdown affected proliferation, migration, and glycolysis in oral CAFs. We found that knockdown of lncRNA H19 by siRNA suppressed the MAPK signaling pathway, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and miR-675-5p. Furthermore, the lncRNA H19/miR-675-5p/PFKFB3 axis was involved in promoting the glycolysis pathway in oral CAFs, as demonstrated by a luciferase reporter system assay and treatment with a miRNA-specific inhibitor. Our study presents a new way to understand glucose metabolism in oral CAFs, theoretically providing a novel biomarker for OSCC molecular diagnosis and a new target for antitumor therapy.
Subject(s)
Humans , Cancer-Associated Fibroblasts/metabolism , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Glycolysis , Head and Neck Neoplasms , MicroRNAs/metabolism , Mouth Neoplasms/genetics , Phosphofructokinase-2/genetics , RNA, Long Noncoding/genetics , Signal Transduction , Tumor MicroenvironmentABSTRACT
Primary and secondary malignant central nervous system [CNS] tumors are devastating invasive tumors able to give rise to many kinds of differentiated tumor cells. Glioblastoma multiform [GBM], is the most malignant brain tumor, in which its growth and persistence depend on cancer stem cells with enhanced DNA damage repair program that also induces recurrence and resists current chemo- and radiotherapies. Unlike non-tumor stem cells, tumor stem cells lack the normal mechanisms that regulate proliferation and differentiation, resulting in uncontrolled production and incomplete differentiation of tumor cells. In current paper recent developments and new researches in the field of brain tumor stem cells have been reviewed
Subject(s)
Stem Cells , Glioblastoma , Glioma , MicroRNAs , Dacarbazine/analogs & derivatives , Adenoviridae , Phosphofructokinase-2 , Microfilament Proteins , Vesicular Transport Proteins , Protein Serine-Threonine Kinases , Receptors, Transforming Growth Factor beta , Protein Kinase C , Tumor Suppressor Protein p53 , Matrix Metalloproteinases , Y-Box-Binding Protein 1 , Nitric Oxide Synthase Type II , Tubulin , ImmunotherapyABSTRACT
OBJECTIVE@#To study the changes of liver phosphofructokinase-2 (PFK-2) level at different postmortem intervals as well as due to different causes of death.@*METHODS@#One hundred and five rats were randomly divided into 3 groups and the rats were sacrificed by either bleeding, suffocating, and neck breaking, respectively. The content of liver PFK-2 at 0, 1, 2, 4, 8, 12 and 24 hours following death were studied using immunohistochemishtry and image analysis.@*RESULTS@#PFK-2 content of the rat's liver in all 3 groups showed a linear decrease at different postmortem intervals with no significant statistical differences found between the different groups.@*CONCLUSION@#PFK-2 level in rat liver appears to decrease linearly in correlation with prolonged PMI.