Panpan Yu, Zouyu Zhao, Qianyu Sun, Bowen Diao, Chongfeng Sun, Yan Wang, Hui Qiao, Hong Li, Ping Yang
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引用次数: 0
Abstract
Protein glycosylation is strongly associated with tumor progression. Glutathione S-transferase omega 1 (GSTO1) is a member of the glutathione S-transferase family. The significance of GSTO1 N-glycosylation in the progression of cervical cancer (CC) has remained elusive. In this study, we investigated the functional significance of GSTO1 N-glycosylation in CC progression. We employed immunohistochemistry to detect the relative expression of evaluating the link between GSTO1 in CC and benign tissues and the overall survival (OS) and progression-free survival (PFS) in CC patients.In vitro and in vivo experiments to detect CC cell proliferation or metastatic ability after GSTO1 downregulation. NetNGly1.0 Server database predicts potential N-glycosylation modification sites of GSTO1 (Asn55, Asn135, Asn190). Investigating GSTO1 N-glycosylation’s function in cellular migration, invasion and epithelial–mesenchymal transition (EMT), we mutated the N-glycosylation sites of GSTO1 through lentivirus-based insertional mutagenesis. Detection of signalling pathways associated with N-glycosylation-modified GSTO1 by enrichment analysis and Western blot. Compared to normal cervical tissue, CC tissue showed significantly higher GSTO1 expression. Further, high GSTO1 levels were a poor predictor of OS and PFS. Both cell and animal experiments suggested that down-regulation of GSTO1 inhibited cell proliferation and metastasis. Glycosylation modification of targeted mutant GSTO1 at positions 55, 135 and 190 significantly inhibits migration and invasion of CC cells. GSTO1 N-glycosylation fixed point mutation inhibits EMT process in CC cells. Mechanistically, N-glycosylated GSTO1 promoted the expression of JAK/STAT3 pathway related markers. GSTO1 N-glycosylation is associated with CC progression and may promote EMT via JAK/STAT3 signaling.
蛋白糖基化与肿瘤进展密切相关。谷胱甘肽s -转移酶- 1 (GSTO1)是谷胱甘肽s -转移酶家族的一员。GSTO1 n -糖基化在宫颈癌(CC)进展中的意义尚不明确。在这项研究中,我们研究了GSTO1 n -糖基化在CC进展中的功能意义。我们采用免疫组织化学检测GSTO1在CC和良性组织中的相对表达,评估GSTO1与CC患者总生存期(OS)和无进展生存期(PFS)之间的关系。体外和体内实验检测GSTO1下调后CC细胞的增殖或转移能力。NetNGly1.0 Server数据库预测GSTO1潜在的n -糖基化修饰位点(Asn55, Asn135, Asn190)。为了研究GSTO1 n -糖基化在细胞迁移、侵袭和上皮间质转化(EMT)中的功能,我们通过慢病毒插入诱变对GSTO1的n -糖基化位点进行了突变。富集分析和Western blot检测n-糖基化修饰GSTO1相关信号通路。与正常宫颈组织相比,CC组织GSTO1表达明显升高。此外,高GSTO1水平是OS和PFS的不良预测因子。细胞和动物实验均表明,下调GSTO1可抑制细胞增殖和转移。靶向突变体GSTO1在55,135和190位点的糖基化修饰可显著抑制CC细胞的迁移和侵袭。GSTO1 n -糖基化定点突变抑制CC细胞的EMT过程。机制上,n -糖基化的GSTO1促进了JAK/STAT3通路相关标志物的表达。GSTO1 n -糖基化与CC进展相关,并可能通过JAK/STAT3信号传导促进EMT。图形抽象
期刊介绍:
Functional & Integrative Genomics is devoted to large-scale studies of genomes and their functions, including systems analyses of biological processes. The journal will provide the research community an integrated platform where researchers can share, review and discuss their findings on important biological questions that will ultimately enable us to answer the fundamental question: How do genomes work?