Rong Zhao, Jiaping Chen, Yangwei Wang, Han Xiao, Peiyuan Mei, Wei Lin, Mingxin Diao, Shiwen He, Yongde Liao, Wangyang Meng
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引用次数: 0
摘要
背景：许多研究已经证明了METTL3蛋白的表达与各种癌症的临床预后之间的关系，并阐明了METTL3扰乱癌细胞行为的机制。在此，我们试图通过系统分析来确定METTL3蛋白在癌症患者中的预后价值，并探索使用特异性抑制剂抑制METTL3的潜在效果：我们在PubMed、Embase和Web of Science数据库中检索了阐明METTL3蛋白表达在所有癌症类型中预后价值的研究，然后计算了所有癌症类型和亚组总生存期（OS）的汇总危险比及95%置信区间。癌症基因组图谱数据集的数据被用于研究癌症中METTL3 mRNA的表达。此外，还通过集落形成试验、细胞增殖试验和细胞凋亡检测，研究了METTL3特异性抑制剂对癌细胞的影响：对32项研究中的33个队列（共3666名患者）进行的元分析表明，METTL3蛋白表达较高表明大多数癌症的OS较差。对METTL3 mRNA表达和癌症预后的生物信息学分析并未显示出METTL3 mRNA极其突出的预后价值。然而，METTL3特异性抑制剂可减轻细胞增殖和细胞克隆形成，促进细胞凋亡：结论：METTL3蛋白表达与大多数癌症类型的不良预后有关，可作为OS的生物标志物。此外，抑制 METTL3 可能是一种潜在的癌症治疗策略。
Prognostic roles of dysregulated METTL3 protein expression in cancers and potential anticancer value by inhibiting METTL3 function
Background
Many studies have demonstrated the relationship between METTL3 protein expression and clinical outcomes in various cancers and elucidated the mechanism by which METTL3 disrupts the behavior of cancer cells. Here, we attempted to define the prognostic value of METTL3 protein in patients with cancer via systematic analysis and explored the potential effect of inhibiting METTL3 using its specific inhibitor.
Methods
We searched PubMed, Embase, and the Web of Science databases for studies that elucidated the prognostic value of METTL3 protein expression in all cancer types and then calculated the pooled hazard ratios with 95% confidence intervals for the overall survival (OS) of all cancer types and subgroups. Data from The Cancer Genome Atlas dataset were used to study METTL3 mRNA expression in cancers. Further, the effects of a METTL3-specific inhibitor were studied in cancer cells via the colony formation assay, the cell proliferation assay, and apoptosis detection.
Results
Meta-analysis of the 33 cohorts in 32 studies (3666 patients in total) revealed that higher METTL3 protein expression indicated poor OS in the majority of cancers. Bioinformatics analysis of METTL3 mRNA expression and cancer prognosis did not show the extremely prominent prognostic value of METTL3 mRNA. Nevertheless, the METTL3-specific inhibitor attenuated cell proliferation and cell cloning formation and promoted apoptosis.
Conclusions
METTL3 protein expression is associated with poor prognosis in most cancer types and could be a biomarker for OS. Further, METTL3 inhibition might be a potential treatment strategy for cancers.
期刊介绍：
Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including:
Antimicrobial, Antiviral Agents
Autonomic Pharmacology
Cardiovascular Pharmacology
Cellular Pharmacology
Clinical Trials
Endocrinopharmacology
Gene Therapy
Inflammation, Immunopharmacology
Lipids, Atherosclerosis
Liver and G-I Tract Pharmacology
Metabolism, Pharmacokinetics
Neuropharmacology
Neuropsychopharmacology
Oncopharmacology
Pediatric Pharmacology Development
Pharmacoeconomics
Pharmacoepidemiology
Pharmacogenetics, Pharmacogenomics
Pharmacovigilance
Pulmonary Pharmacology
Receptors, Signal Transduction
Renal Pharmacology
Thrombosis and Hemostasis
Toxicopharmacology
Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.
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