MCTS1再起始和释放因子(MCTS1)在一些癌症中被表征为癌蛋白。在这项研究中,我们探讨了MCTS1在喉鳞状细胞癌(LSCC)中的表达及其对肿瘤细胞增殖和细胞周期进程的调节作用,以及潜在的机制。来自癌症基因组图谱的数据用于分析MCTS1表达及其与LSCC患者生存结果的相关性。基于代表性的LSCC细胞系进行随后的体外细胞和分子研究。结果显示,LSCC中MCTS1的上调与无进展生存期(PFS)和疾病特异性生存期(DSS)较差有关。在TU177和AMC-HN-8细胞中,MCTS1对细胞活力有正向调控作用,菌落形成,细胞周期进程,以及CDK1,CDK2,细胞周期蛋白A2和细胞周期蛋白B1的表达。Co-IP测定证实MCTS1和LARP7之间的相互作用,主要在细胞质中。环己酰亚胺(CHX)追踪和co-IP泛素化分析显示,MCTS1可增加LARP7蛋白的半衰期,减少其聚泛素化。LARP7过表达增强了LSCC细胞的活力和集落形成,并提高了CDK1,CDK2,细胞周期蛋白A2和细胞周期蛋白B1的表达。此外,其过度表达部分逆转了MCTS1敲低的负面影响。总之,这项研究证实MCTS1的表达可能是LSCC患者预后不良的指标.机械上,它通过与LARP7相互作用并减少其蛋白酶体介导的降解来促进LSCC细胞的活力和增殖。
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.