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Differential Expression and Copy Number Variation of Gasdermin (GSDM) Family Members, Pore-Forming Proteins in Pyroptosis, in Normal and Malignant Serous Ovarian Tissue
Inflammation ( IF 5.1 ) Pub Date : 2021-06-06 , DOI: 10.1007/s10753-021-01493-0
Caglar Berkel 1 , Ercan Cacan 1
Affiliation  

Gasdermins (GSDM) are members of a family of pore-forming effector proteins which lead to membrane permeabilization and pyroptosis, a lytic cell death with pro-inflammatory characteristics. Recently, two members of the gasdermin family, gasdermin B (GSDMB) and gasdermin E (GSDME), were shown to suppress tumor growth, through the involvement of cytotoxic lymphocytes. Other studies also reported the important functions of gasdermins in various cancer types including gastric cancer, hepatocarcinoma, and cervix and breast cancer. However, gasdermins have not been previously studied in the context of serous ovarian cancer. Here, we showed that gasdermin D (GSDMD) and gasdermin C (GSDMC) expression increases in serous ovarian cancer; in contrast, the expression of GSDME and PJVK (Pejvakin, DFNB59) is downregulated, compared to healthy ovaries, in multiple independent gene expression datasets. We found that copy number gains are highly frequent (present in approximately 50% of patients) in genes encoding GSDMD and GSDMC in ovarian cancer, in line with their upregulated expression in serous ovarian cancer. Moreover, we observed that the expression of GSDMB and GSDMD, but not of GSDME, is different among several histotypes of epithelial ovarian cancer. Therefore, we propose that differential expression and copy number variations of certain gasdermins might be associated with the development of serous ovarian cancer, in which different members of the family have distinct functions; however, further research is required in in vivo models to understand how changes in gasdermin family members mechanistically contribute to serous ovarian cancer.



中文翻译:

Gasdermin (GSDM) 家族成员的差异表达和拷贝数变异,细胞焦亡中的成孔蛋白,在正常和恶性浆液性卵巢组织中

Gasdermins (GSDM) 是成孔效应蛋白家族的成员,可导致膜透化和细胞焦亡,这是一种具有促炎特征的裂解细胞死亡。最近,gasdermin 家族的两个成员,gasdermin B (GSDMB) 和 gasdermin E (GSDME),被证明通过细胞毒性淋巴细胞的参与来抑制肿瘤生长。其他研究还报道了gasdermins在各种癌症类型中的重要作用,包括胃癌、肝癌、宫颈癌和乳腺癌。然而,以前没有在浆液性卵巢癌的背景下研究过gasdermins。在这里,我们发现gasdermin D (GSDMD) 和gasdermin C (GSDMC) 在浆液性卵巢癌中的表达增加。相比之下,与健康卵巢相比,GSDME 和 PJVK (Pejvakin, DFNB59) 的表达下调,在多个独立的基因表达数据集中。我们发现在卵巢癌中编码 GSDMD 和 GSDMC 的基因中拷贝数增加非常频繁(存在于大约 50% 的患者中),这与它们在浆液性卵巢癌中的上调表达一致。此外,我们观察到 GSDMB 和 GSDMD 的表达,而不是 GSDME 的表达,在上皮性卵巢癌的几种组织型中是不同的。因此,我们提出某些gasdermins的差异表达和拷贝数变异可能与浆液性卵巢癌的发展有关,其中不同的家族成员具有不同的功能。然而,还需要进一步研究 我们发现在卵巢癌中编码 GSDMD 和 GSDMC 的基因中拷贝数增加非常频繁(存在于大约 50% 的患者中),这与它们在浆液性卵巢癌中的上调表达一致。此外,我们观察到 GSDMB 和 GSDMD 的表达,而不是 GSDME 的表达,在上皮性卵巢癌的几种组织型中是不同的。因此,我们提出某些gasdermins的差异表达和拷贝数变异可能与浆液性卵巢癌的发展有关,其中不同的家族成员具有不同的功能。然而,还需要进一步研究 我们发现在卵巢癌中编码 GSDMD 和 GSDMC 的基因中拷贝数增加非常频繁(存在于大约 50% 的患者中),这与它们在浆液性卵巢癌中的上调表达一致。此外,我们观察到 GSDMB 和 GSDMD 的表达,而不是 GSDME 的表达,在上皮性卵巢癌的几种组织型中是不同的。因此,我们提出某些gasdermins的差异表达和拷贝数变异可能与浆液性卵巢癌的发展有关,其中不同的家族成员具有不同的功能。然而,还需要进一步研究 在上皮性卵巢癌的几种组织型中是不同的。因此,我们提出某些gasdermins的差异表达和拷贝数变异可能与浆液性卵巢癌的发展有关,其中不同的家族成员具有不同的功能。然而,还需要进一步研究 在上皮性卵巢癌的几种组织型中是不同的。因此,我们提出某些gasdermins的差异表达和拷贝数变异可能与浆液性卵巢癌的发展有关,其中不同的家族成员具有不同的功能。然而,还需要进一步研究体内模型,以了解gasdermin家族成员的变化如何机械地导致浆液性卵巢癌。

更新日期:2021-06-07
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