BST2 regulated by the transcription factor STAT1 can promote metastasis, invasion and proliferation of oral squamous cell carcinoma via the AKT/ERK1/2 signaling pathway.

Oral squamous cell carcinoma (OSCC) is one of the main types of head and neck squamous cell carcinoma. Although progress has been made in treating OSCC, it remains a threat to human health, and novel therapeutic strategies are needed to extend the lifespan of patients with OSCC. The present study, evaluated whether bone marrow stromal antigen 2 (BST2) and STAT1 were potential therapeutic targets in OSCC. Small interfering RNA (siRNA) or overexpression plasmids were used to regulate BST2 or STAT1 expression. Western blotting and reverse transcription­quantitative PCR were performed to assess changes in the protein and mRNA expression levels of signaling pathway components. The effects of BST2 and STAT1 expression changes on the migration, invasion and proliferation of OSCC cells were assessed using the scratch test assay, Transwell assay and colony formation assay in vitro, respectively. Cell­derived xenograft models were used to evaluate the impact of BST2 and STAT1 on the occurrence and development of OSCC in vivo. Finally, it was demonstrated that BST2 expression was significantly upregulated in OSCC. Furthermore, it was demonstrated that high expression of BST2 in OSCC contributed to the metastasis, invasion and proliferation of OSCC cells. Moreover, it was demonstrated that the promoter region of BST2 was regulated by the transcription factor STAT1, and that the STAT1/BST2 axis could affect the behavior of OSCC via the AKT/ERK1/2 signaling pathway. In vivo studies also demonstrated that STAT1 downregulation inhibited OSCC growth by down­regulating BST2 expression via the AKT/ERK1/2 signaling pathway.

LAMC2 regulates proliferation, migration, and invasion mediated by the Pl3K/AKT/mTOR pathway in oral.

Background: Oral squamous cell carcinoma (OSCC) is a common malignant tumor. Recently, Laminin Gamma 2 (LAMC2) has been shown to be abnormally expressed in OSCC; however, how LAMC2 signaling contributes to the occurrence and development of OSCC and the role of autophagy in OSCC has not been fully explored. This study aimed to analyze the role and mechanism of LAMC2 signaling in OSCC and the involvement of autophagy in OSCC. Methods: To explore the mechanism by which LAMC2 is highly expressed in OSCC, we used small interfering RNA (siRNA) to knock down LAMC2 to further observe the changes in the signaling pathway. Furthermore, we used cell proliferation assays, Transwell invasion assays, and wound-healing assays to observe the changes in OSCC proliferation, invasion, and metastasis. RFP-LC3 was used to detect the level of autophagy intensity. A cell line-derived xenograft (CDX) model was used to detect the effect of LAMC2 on tumor growth in vivo. Results: This study found that the level of autophagy was correlated with the biological behavior of OSCC. The downregulation of LAMC2 activated autophagy and inhibited OSCC proliferation, invasion, and metastasis via inhibiting the PI3K/AKT/mTOR pathway. Moreover, autophagy has a dual effect on OSCC, and the synergistic downregulation of LAMC2 and autophagy can inhibit OSCC metastasis, invasion, and proliferation via the PI3K/AKT/mTOR pathway. Conclusions: LAMC2 interacts with autophagy to regulate OSCC metastasis, invasion, and proliferation via the PI3K/AKT/mTOR pathway. LAMC2 down-regulation can synergistically modulate autophagy to inhibit OSCC migration, invasion, and proliferation.

Rapamycin Inhibits Osteoclastogenesis and Prevents LPS-Induced Alveolar Bone Loss by Oxidative Stress Suppression.

Periodontitis is a progressive inflammatory skeletal disease characterized by periodontal tissue destruction, alveolar bone resorption, and tooth loss. Chronic inflammatory response and excessive osteoclastogenesis play essential roles in periodontitis progression. Unfortunately, the pathogenesis that contributes to periodontitis remains unclear. As a specific inhibitor of the mTOR (mammalian/mechanistic target of rapamycin) signaling pathway and the most common autophagy activator, rapamycin plays a vital role in regulating various cellular processes. The present study investigated the effects of rapamycin on osteoclast (OC) formation in vitro and its effects on the rat periodontitis model. The results showed that rapamycin inhibited OC formation in a dose-dependent manner by up-regulating the Nrf2/GCLC signaling pathway, thus suppressing the intracellular redox status, as measured by 2',7'-dichlorofluorescein diacetate and MitoSOX. In addition, rather than simply increasing the autophagosome formation, rapamycin increased the autophagy flux during OC formation. Importantly, the anti-oxidative effect of rapamycin was regulated by an increase in autophagy flux, which could be attenuated by blocking autophagy with bafilomycin A1. In line with the in vitro results, rapamycin treatment attenuated alveolar bone resorption in rats with lipopolysaccharide-induced periodontitis in a dose-dependent manner, as assessed by micro-computed tomography, hematoxylin-eosin staining, and tartrate-resistant acid phosphatase staining. Besides, high-dose rapamycin treatment could reduce the serum levels of proinflammatory factors and oxidative stress in periodontitis rats. In conclusion, this study expanded our understanding of rapamycin's role in OC formation and protection from inflammatory bone diseases.

Correction to "Rapamycin Inhibits Osteoclastogenesis and Prevents LPS-Induced Alveolar Bone Loss by Oxidative Stress Suppression".

[This corrects the article DOI: 10.1021/acsomega.3c01289.].