KAT2A-mediated succinylation modification of notch1 promotes the proliferation and differentiation of dental pulp stem cells by activating notch pathway.

BACKGROUND: Dental pulp stem cells (DPSCs) are a kind of undifferentiated dental mesenchymal stem cells with strong self-renewal ability and multi-differentiation potential. This study aimed to investigate the regulatory functions of succinylation modification in DPSCs. METHODS: DPSCs were isolated from the dental pulp collected from healthy subjects, and then stem cell surface markers were identified using flow cytometry. The osteogenic differentiation ability of DPSCs was verified by alkaline phosphatase (ALP) and alizarin red staining methods, while adipogenic differentiation was detected by oil red O staining. Meanwhile, the mRNA of two desuccinylases (SIRT5 and SIRT7) and three succinylases (KAT2A, KAT3B, and CPT1A) in DPSCs before and after mineralization induction were detected using quantitative real-time PCR. The cell cycle was measured by flow cytometry, and the expression of bone-specific genes, including COL1a1 and Runx2 were evaluated by western blotting and were combined for the proliferation and differentiation of DPSCs. Co-immunoprecipitation (co-IP) and immunofluorescence were combined to verify the binding relationship between proteins. RESULTS: The specific markers of mesenchymal stem cells were highly expressed in DPSCs, while the osteogenic differentiation ability of isolated DPSCs was confirmed via ALP and alizarin red staining. Similarly, the oil red O staining also verified the adipogenic differentiation ability of DPSCs. The levels of KAT2A were found to be significantly upregulated in mineralization induction, which significantly decreased the ratio of G0/G1 phase and increased S phase cells; converse results regarding cell cycle distribution were obtained when KAT2A was inhibited. Moreover, overexpression of KAT2A promoted the differentiation of DPSCs, while its inhibition exerted the opposite effect. The elevated KAT2A was found to activate the Notch1 signaling pathway, which succinylated Notch1 at the K2177 site to increase their corresponding protein levels in DPSCs. The co-IP results showed that KAT2A and Notch1 were endogenously bound to each other, while inhibition of Notch1 reversed the effects of KAT2A overexpression on the DPSCs proliferation and differentiation. CONCLUSION: KAT2A interacted directly with Notch1, succinylating the Notch1 at the K2177 site to increase their corresponding protein levels in DPSCs. Similarly, KAT2A-mediated succinylation modification of Notch1 promotes the DPSCs proliferation and differentiation, suggesting that targeting KAT2A and Notch1 may contribute to tooth regeneration.

Role of c-Met expression on prognosis of head and neck cancer: A literature review and meta-analysis.

The prognostic role of c-Met expression in patients with head and neck cancer were controversial among different studies. Thus, we performed a meta-analysis to evaluate the relationships between c-Met expression and survival and clinical parameters of head and neck cancer patients. Summary hazard ratio (HR) and 95% confidence intervals (CIs) were calculated to analyze the correlations between c-Met expression and overall survival (OS), and disease-free survival (DFS). Furthermore, odds ratios (ORs) and 95% CIs were used to describe the relationships between c-Met expression and different clinicopathological parameters. A total of 2417 patients from 19 studies were enrolled in the final analysis. The results showed that patients with higher c-Met expression had a poor OS (HR, 1.65; 95% CI, 1.20-2.27) and DFS (HR, 1.48; 95% CI, 0.99-2.20). In addition, c-Met expression was associated with the N classification of patients with head and neck cancer. These results suggested that c-Met expression was a risk factor for head and neck cancer, and increased c-Met expression would be a predictor of a poorer prognosis for the patients.

Synergistic anticancer effects of nanocarrier loaded with berberine and miR-122.

We introduced polyethyleneimine (PEI)-cholesterol (PC) as a nanocarrier incorporating berberine (BER) and miR-122 for the treatment of oral squamous cell carcinoma (OSCC). BER was stabilized by incorporating PC to form ber-PC. Ber-PC was further electrostatically complexed with miR-122 to yield mr-ber-PC for the co-delivery of BER and miR-122. mr-ber-PC treatment dramatically decreased the level of invasion and migration of OSCC cells compared with single drug treatments. The present study suggested that PC could be a multifunctional nanocarrier for the co-delivery of anticancer drug BER and miR-122 to significantly increase the anticancer therapeutic effects.

Antineoplastic activity of Newcastle disease virus strain D90 in oral squamous cell carcinoma.

Newcastle disease virus (NDV), an avian paramyxovirus, possesses the ability to kill tumor cells. Here, we report the effects of NDV strain D90, which was isolated in China, against oral squamous cell carcinoma (OSCC) cells. In this study, we showed that the cell death induced by D90 was apoptotic. Furthermore, the apoptosis induced by D90 was dependent on the mitochondrial pathway, and the death receptor pathway may be not involved. Bax and Bcl-2 also played a role in the apoptosis induced by D90. Lymph node metastasis is a serious problem for oral cancer; we therefore evaluated the impact of D90 on the migration and invasion of OSCC cells. NDV D90 affected microtubules and microfilaments to inhibit the motility of OSCC prior to apoptosis. The effects of D90 on the migration and invasion rates of OSCC cells were evaluated by migration and invasion assays. Subsequently, the changes in sp1, RECK, MMP-2, and MMP-9 induced by a low concentration of D90 were detected by western blot and gelatin zymography. D90 significantly inhibited the invasion and metastasis of OSCC cells by decreasing the expression of sp1 and increasing the expression of RECK to suppress the expression and activity of MMP-2 and MMP-9.