ABSTRACT
BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor of the nasopharyngeal mucosa with a high incidence rate all over the world. Methyltransferase-like 14 (METTL14) is a major RNA N6-adenosine methyltransferase implicated in tumor progression by regulating RNA function. This study is designed to explore the biological function and mechanism of METTL14 in NPC. METHODS: METTL14 and Amine oxidase copper containing 1 (AOC1) expression were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The protein levels of METTL14, AOC1, Cyclin D1, B-cell lymphoma-2 (Bcl-2), and N-cadherin were measured using western blot. Cell proliferation, cycle progression, apoptosis, migration, and invasion were assessed using 5-ethynyl-2'-deoxyuridine (EdU), Colony formation, flow cytometry, wound scratch, and transwell assays. The interaction between METTL14 and AOC1 was verified using RNA immunoprecipitation (RIP), methylated RNA immunoprecipitation (MeRIP), and dual-luciferase reporter assays. The biological role of METTL14 on NPC tumor growth was examined by the xenograft tumor model in vivo. RESULTS: METTL14 and AOC1 were highly expressed in NPC tissues and cells. Moreover, METTL14 knockdown might block NPC cell proliferation, migration, invasion, and induce cell apoptosis in vitro. In mechanism, METTL14 might enhance the stability of AOC1 mRNA via m6A methylation. METTL14 silencing might repress NPC tumor growth in vivo. CONCLUSION: METTL14 might boosted the development of NPC cells partly by regulating the stability of AOC1 mRNA, which provided a promising therapeutic target for NPC treatment.
Subject(s)
Cell Proliferation , Gene Expression Regulation, Neoplastic , Methyltransferases , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , RNA Stability , RNA, Messenger , Humans , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/metabolism , Methyltransferases/genetics , Methyltransferases/metabolism , Cell Line, Tumor , Animals , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/metabolism , RNA, Messenger/genetics , Apoptosis/genetics , Mice , Cell Movement , Disease Progression , Male , FemaleABSTRACT
The aim of this study was to assess the risk of sarcopenia and osteoporosis in elderly patients with obstructive sleep apnea syndrome (OSAS). We recruited both OSAS patients and non-OSAS subjects from multiple centers and evaluated their skeletal muscle index (SMI), bone mineral density (BMD), and inflammatory factors. All participants underwent polysomnography (PSG) testing, handgrip strength testing, chest CT, and dual-energy x-ray BMD testing. Based on the PSG diagnosis results, the participants were divided into a control group and an OSAS group. The analysis results revealed a higher incidence of sarcopenia in the OSAS group (χ2â¯=â¯22.367; Pâ¯=â¯0.000) and osteoporosis (χ2â¯=â¯11.730a; Pâ¯=â¯0.001). There were statistically significant differences in BMI (Pâ¯=â¯0.000), grip strength (Pâ¯=â¯0.000), SMI (Pâ¯=â¯0.000), bone density (Pâ¯=â¯0.000) and vitamin D (Pâ¯=â¯0.000). The independent sample t test results showed that there was no statistical difference between IL-6 (Pâ¯=â¯0.247) and CRP (Pâ¯=â¯0.246). Considering the potential impact of body weight on the observed indicators, we employed covariance analysis to calculate the modified P value for each observation indicator. The findings demonstrated that the grip strength, IL-6, and CRP levels in the OSAS group were significantly higher compared to the control group. Conversely, the SMI, bone density, and Vitamin D levels were found to be significantly lower in the OSAS group than in the control group. These results suggest a higher likelihood of sarcopenia and osteoporosis among OSAS patients. Further studies should be conducted in larger study populations.
