Knockdown of PGC1α suppresses dysplastic oral keratinocytes proliferation through reprogramming energy metabolism / 国际口腔科学杂志·英文版

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.

Single-photon emission computed tomography for the diagnosis of mandibular invasion caused by oral cancers: a systematic review and Meta-analysis / 华西口腔医学杂志

Objective This review aimed at assessing the diagnostic efficacy of contrast-enhanced single-photon emission computed tomography (SPECT) in the diagnosis of mandibular invasion by oral cancers. Methods Five databases were searched electronically on August 5, 2016. The reference lists of included studies were hand searched. Quality assessment was performed by two reviewers in duplicate with tools suggested by Cochrane's handbook. Furthermore, the data extraction of included studies was delivered. Meta-analysis was performed using STATA 11.0. Results Ten studies with 460 participants were included. One study had a low risk of bias, and two studies had a high risk of bias. The remaining seven studies had an unclear risk of bias. Meta-analysis results showed that SPECT had a pooled sensitivity of 0.99 [95% confidence interval=0.87-
1.00]. Sensitivity was 0.99 on Q* point. The specificity of 0.61 and the area under summary receiver operating characteristic curve (SROC) were 0.93 [95% confidence interval=0.90-
0.95]. The pooled positive likelihood ratio was 2.555. The negative likelihood ratio was 0.015. The diagnostic odd ratio was 5.115. Conclusion SPECT had high sensitivity, which became suitable for excluding bone invasion by oral cancers. However, its specificity was relatively low, indicating its limited capability in confirming diagnosis. Therefore, surgeons should perform this method under certain conditions.