Exosomes Laboratory and Metabolomics Platform, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), 48160 Derio, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas Y Digestivas (CIBERehd), 28029 Madrid, Spain.
Int J Mol Sci. 2023 Oct 27;24(21):15668. doi: 10.3390/ijms242115668.
The human CERS2 gene encodes a ceramide synthase enzyme, known as CERS2 (ceramide synthase 2). This protein is also known as LASS2 (LAG1 longevity assurance homolog 2) and TMSG1 (tumor metastasis-suppressor gene 1). Although previously described as a tumor suppressor for different types of cancer, such as prostate or liver cancer, it has also been observed to promote tumor growth in adenocarcinoma. In this review, we focus on the influence of CERS2 in bladder cancer (BC), approaching the existing literature about its structure and activity, as well as the miRNAs regulating its expression. From a mechanistic point of view, different explanations for the role of CERS2 as an antitumor protein have been proposed, including the production of long-chain ceramides, interaction with vacuolar ATPase, and its function as inhibitor of mitochondrial fission. In addition, we reviewed the literature specifically studying the expression of this gene in both BC and biopsy-derived tumor cell lines, complementing this with an analysis of public gene expression data and its association with disease progression. We also discuss the importance of CERS2 as a biomarker and the presence of CERS2 mRNA in extracellular vesicles isolated from urine.
人类 CERS2 基因编码一种神经酰胺合酶酶，称为 CERS2（神经酰胺合酶 2）。这种蛋白质也被称为 LASS2（LAG1 长寿保证同源物 2）和 TMSG1（肿瘤转移抑制基因 1）。尽管先前被描述为不同类型癌症（如前列腺癌或肝癌）的肿瘤抑制因子，但也观察到它在腺癌中促进肿瘤生长。在这篇综述中，我们专注于 CERS2 在膀胱癌（BC）中的影响，探讨其结构和活性以及调节其表达的 miRNAs 的现有文献。从机制的角度来看，已经提出了 CERS2 作为抗肿瘤蛋白的作用的不同解释，包括长链神经酰胺的产生、与液泡型 ATP 酶的相互作用以及作为线粒体分裂抑制剂的功能。此外，我们还专门综述了该基因在 BC 和活检衍生的肿瘤细胞系中的表达情况，并补充了对公共基因表达数据的分析及其与疾病进展的关联。我们还讨论了 CERS2 作为生物标志物的重要性以及从尿液中分离的细胞外囊泡中存在 CERS2 mRNA。
