RESUMEN
Glioma is a primary brain tumor with limited treatment approaches and glioblastoma stem cells (GSCs) are manifested with the self-renewal capability and high tumorigenic capacity. This study was performed to investigate the regulatory effect of the SUMO-specific protease 1 (SENP1)/methyltransferase-like 3 (METTL3)/MYC axis on the self-renewal of GSCs mediated by transcription factor Yin Yang 1 (YY1). Following bioinformatics analysis and clinical and cellular experiments, we found that YY1 was highly expressed in GBM tissues and cells, while silencing its expression reduced the self-renewal ability of GSCs. Functionally, YY1 promoted the transcriptional expression of SENP1 by binding to the promoter region of SENP1, while the deSUMOase SENP1 facilitated the methylase activity of m6A through deSUMOylation of the methylase METTL3, thereby promoting the m6A modification of MYC mRNA via METL3 and promoting the expression of MYC. A nude mouse xenograft model of GBM was also constructed to examine the tumorigenicity of GSCs. The obtained findings demonstrated that YY1 promoted tumorigenicity of GSCs by promoting the expression of MYC in vivo. Conclusively, YY1 can transcriptionally upregulate the SUMOylase SENP1 and enhance the methylase activity of METTL3, resulting in the increased m6A modification level of MYC mRNA, thereby promoting the self-renewal of GSCs.
Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Animales , Ratones , Humanos , Glioblastoma/patología , Factor de Transcripción YY1/genética , Factor de Transcripción YY1/metabolismo , Péptido Hidrolasas/metabolismo , Células Madre Neoplásicas/patología , ARN Mensajero/metabolismo , Neoplasias Encefálicas/genética , Proliferación Celular/genética , Línea Celular Tumoral , Metiltransferasas/metabolismo , Cisteína Endopeptidasas/genética , Cisteína Endopeptidasas/metabolismoRESUMEN
BACKGROUND: Wnt/β-catenin signaling pathway plays a vital role in the development of osteoarthritis. OBJECTIVE: To review the recent progress of treating osteoarthritis based on the Wnt/β-catenin signaling pathway. METHODS: An electronical literature retrieval of PubMed, CNKI and WanFang databases was performed to search the literatures concerning the Wnt/β-catenin pathway in the treatment of osteoarthritis. The keywords were “catenin; wnt; osteoarthritis; arthritis; degenerative; arthritides; deformans; pathway; wnt signaling; signaling pathway; wnt signaling pathways; wnt beta catenin signaling pathway; canonical wnt pathway; canonical wnt” in English and Chinese, respectively. Finally, 74 articles were included in result analysis. RESULTS AND CONCLUSION: The potential treatments of osteoarthritis based on the Wnt/β-Catenin signal pathway include natural antagonists, small molecule inhibitors, agonists, traditional Chinese medicine and drug reposition. These drug pathways provide chondroprotective effect via activating or inhibiting the Wnt/β-catenin signaling pathway. The treatment of osteoarthritis based on the Wnt/β-catenin signaling pathway is currently in the laboratory stage, but it has a great application prospect. How to accurately regulate the pathway and better transfer the research results into the application will become a hotspot in the future.