RÉSUMÉ
Oral potentially malignant disorders (OPMDs) are precursors of oral squamous cell carcinoma (OSCC). Deregulated cellular energy metabolism is a critical hallmark of cancer cells. Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1α) plays vital role in mitochondrial energy metabolism. However, the molecular mechanism of PGC1α on OPMDs progression is less unclear. Therefore, we investigated the effects of knockdown PGC1α on human dysplastic oral keratinocytes (DOKs) comprehensively, including cell proliferation, cell cycle, apoptosis, xenograft tumor, mitochondrial DNA (mtDNA), mitochondrial electron transport chain complexes (ETC), reactive oxygen species (ROS), oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and glucose uptake. We found that knockdown PGC1α significantly inhibited the proliferation of DOKs in vitro and tumor growth in vivo, induced S-phase arrest, and suppressed PI3K/Akt signaling pathway without affecting cell apoptosis. Mechanistically, downregulated of PGC1α decreased mtDNA, ETC, and OCR, while enhancing ROS, glucose uptake, ECAR, and glycolysis by regulating lactate dehydrogenase A (LDHA). Moreover, SR18292 (an inhibitor of PGC1α) induced oxidative phosphorylation dysfunction of DOKs and declined DOK xenograft tumor progression. Thus, our work suggests that PGC1α plays a crucial role in cell proliferation by reprograming energy metabolism and interfering with energy metabolism, acting as a potential therapeutic target for OPMDs.
Sujet(s)
Humains , Carcinome épidermoïde/métabolisme , Prolifération cellulaire , ADN mitochondrial , Métabolisme énergétique , Glucose , Tumeurs de la bouche/métabolisme , Coactivateur 1-alpha du récepteur gamma activé par les proliférateurs de peroxysomes/métabolisme , Phosphatidylinositol 3-kinases , Espèces réactives de l'oxygèneRÉSUMÉ
Forensic science is looking for clues at a crime scene in order to reconstruct the crime scene.Classic clues include DNA and fingerprints.Forensic microbiology is a branch of forensic medicine that uses microbes as clues,providing us information about lifestyle,circadian rhythms,geographic locations,postmortem intervals,cancers,and oral or systemic diseases.Oral cavity,as the place with the second largest number of microorganisms,can provide researchers with microbial information of each ecological niche,and assist in the prediction,diagnosis and monitoring of oral or systemic diseases.This paper reviews the composition of oral microbiome,the application in oral diseases,systemic diseases and forensic medicine,with the aim of providing some references for the development of forensic microbiology based on oral microbiome.