RESUMO
The aberrant upregulation of MCTS1 Re-Initiation and Release Factor (also known as Malignant T-cell-amplified sequence 1, MCTS1) can promote laryngeal squamous cell carcinoma (LSCC). It might act as a binding partner of multiple proteins. In this study, we further explored the expression of potential interaction between MCTS1 and OTU domain-containing protein 6B (OTUD6B) and its influence on the ubiquitination and degradation of OTUD6B's substrate in LSCC. LSCC cell lines AMC-HN-8 and TU177 were utilized for assessing protein-protein interaction, protein degradation and tumor growth in vitro and in vivo. The results showed that MCTS1 interacts with OUTD6B isoform 1 (OTUD6B-1) in the cell lines. Higher OTUD6B-1 expression is associated with significantly shorter progression-free interval in LSCC patients. OTUD6B positively modulated the expression of cyclin D1, cyclin E1 and c-Myc and LSCC cell proliferation in vitro and in vivo. MCTS1 negatively modulated the degradation of LIN28B in G1/S cells, via enhancing OTUD6B-mediated cleaving of K48-branched ubiquitin chains from LIN28B. OTUD6B or LIN28B shRNA weakened MCTS1 overexpression-induced cyclin D1 and c-Myc protein expression and LSCC cell proliferation. In summary, this study revealed that MCTS1 could enhance LSCC proliferation partially via the OTUD6B-LIN28B axis.
Assuntos
Ciclina D1 , Neoplasias de Cabeça e Pescoço , Humanos , Proteínas de Ciclo Celular , Linhagem Celular , Proliferação de Células , Proteínas Oncogênicas , Proteínas de Ligação a RNA , Carcinoma de Células Escamosas de Cabeça e Pescoço/genéticaRESUMO
MCTS1 Re-Initiation and Release Factor (MCTS1) has been characterised as an oncoprotein in some cancers. In this study, we explored the expression of MCTS1 in laryngeal squamous cell carcinoma (LSCC) and its regulatory effects on the proliferation and cell-cycle progression of tumour cells, as well as the underlying mechanisms. The data from the Cancer Genome Atlas was used to analyse MCTS1 expression and its correlation with survival outcomes in LSCC patients. Subsequent in vitro cellular and molecular studies were performed based on representative LSCC cell lines. Results showed that the upregulation of MCTS1 in LSCC is linked to poor progression-free survival (PFS) and disease-specific survival (DSS). In TU177 and AMC-HN-8 cells, MCTS1 exerted positive regulations on cell viability, colony formation, cell cycle progression, and the expression of CDK1, CDK2, cyclin A2, and cyclin B1. Co-IP assay confirmed mutual interaction between MCTS1 and LARP7, mainly in the cytoplasm. Cycloheximide (CHX) chase and co-IP assay of ubiquitination showed that MCTS1 could increase LARP7 protein half-life and reduce its poly-ubiquitination. LARP7 overexpression enhanced the viability and colony formation of LSCC cells and also elevated the expression of CDK1, CDK2, cyclin A2, and cyclin B1. In addition, its overexpression partly reversed the negative influence of MCTS1 knockdown. In summary, this study confirmed that the expression of MCTS1 might be an indicator of unfavourable prognosis for patients with LSCC. Mechanically, it promotes LSCC cell viability and proliferation via interacting with LARP7 and reducing its proteasomal-mediated degradation.
Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , MicroRNAs , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Ciclina A2/genética , Ciclina A2/metabolismo , Ciclina B1/genética , Ciclina B1/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patologia , MicroRNAs/genética , Proteínas Oncogênicas/metabolismo , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genéticaRESUMO
Objective:To study the clinical anatomy of the sphenopalatine foramina by dissecting the sphenopalatine foramina during Vidian nerve branch neurotomy. The anatomy and CBCT images of sphenopalatine foramen were analyzed to facilitate the navigational of clinical operation using CBCT images. Methods:From October 2017 to September 2023, 84 casesï¼168 sidesï¼ of Vidian nerve branch neurotomy in our department were collected. The clinical summary was made according to the anatomy of sphenopalatine foramen during the operation. Preoperative CBCT imaging findings of the sphenopalatine foramina were also studied. Results:The clinical anatomy of sphenopalatine foramen could be divided into four types: middle meatus typeï¼1.19%ï¼, trans-meatus typeï¼62.29%ï¼, superior meatus typeï¼33.33%ï¼ and double foramen typeï¼1.19%ï¼. The incidence of ethmoidal ridge was 98.81%. The distance from sphenopalatine foramina to posterior nasal canal wereï¼14.63±2.66ï¼ mm to left andï¼14.65±2.63ï¼ mm to right, The position Angle â a of lower margin of sphenopalatine foramina wereï¼62.36±10.05ï¼° to left andï¼61.51±11.82ï¼° to right, respectively. Axial CT images can be used to divide the sphenopalatine foramen into five levels: the upper edge of the sphenopalatine foramen level, the Vidian nerve level, the basal plate interaction level, the lower edge of the sphenopalatine foramen level and the pterygopalatine canal level. The agreement between endoscopic anatomy of sphenopalatine foramen and imaging navigation was 100%. Conclusion:The sphenopalatine foramina exhibit various anatomical types. The preoperative navigational CBCT reading can effectively identify the type of sphenopalatine foramina, guide the choice of surgical method, and help avoid serious complications. This has significant clinical application value.
Assuntos
Tomografia Computadorizada de Feixe Cônico , Endoscopia , Humanos , Tomografia Computadorizada de Feixe Cônico/métodos , Endoscopia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Osso Esfenoide/diagnóstico por imagem , Osso Esfenoide/anatomia & histologia , Adulto , Cavidade Nasal/diagnóstico por imagem , Cavidade Nasal/anatomia & histologiaRESUMO
The presence of cervical lymph node metastases has been considered as the most important adverse prognostic factor for patients with laryngeal squamous cell carcinoma (LSCC). However, the underlying mechanisms remain to be fully revealed. In this study, we explored the expression profile of Foxhead box D1 (FOXD1), its association with epithelial-to-mesenchymal transition (EMT), and its downstream targets in LSCC. Bioinformatic analysis was performed based on the LSCC subset of The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma (TCGA-HSNC) and Chromatin immunoprecipitation (ChIP)-seq data from Cistrome Data Browser. LSCC cell lines AMC-HN-8 and TU212 were used for in vitro studies. Results showed that FOXD1 upregulation was associated with poor prognosis of LSCC. FOXD1 knockdown reduced N-cadherin and Vimentin expression but increased E-cadherin expression in AMC-HN-8 cells. Its overexpression showed opposite effects in TU212 cells. FOXD1 could bind to the promoter of ZNF532 and activate its transcription. ZNF532 overexpression enhanced the invasion of both AMC-HN-8 and TU212 cells. In comparison, its knockdown significantly impaired their invasion. ZNF532 knockdown nearly abrogated the alterations of EMT markers caused by FOXD1 overexpression. Its overexpression largely rescued the phenotypes caused by FOXD1 knockdown. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that ZNF532 correlated genes are largely enriched in extracellular matrix regulations. LSCC patients with high ZNF532 expression (top 50%) had a significantly worse progression-free survival. In summary, this study confirmed that FOXD1 promotes partial-EMT of LSCC cells via transcriptionally activating the expression of ZNF532.