TRIP 13-dependent pathways promote the development of gastric cancer

IF 3.9 4区 生物学 Q1 GENETICS & HEREDITY Functional & Integrative Genomics Pub Date : 2023-07-11 DOI:10.1007/s10142-023-01160-7
Fengming Ni, Xinmin Liu, Yan Xia, He Zhu, Fudong Li, Nan Zhang, Hong Xu
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Abstract

TRIP13 is highly expressed in various human tumors and promotes tumorigenesis. We aimed to explore the biological effect of TRIP13 on gastric cancer. The RNA sequence data were retrieved from TCGA to evaluate TRIP13 mRNA expression in gastric cancer. Paired formalin-fixed paraffin-embedded blocks were further analyzed to verify the relationship between TRIP13 expression and carcinogenic status. The functions of TRIP13 on the proliferation of gastric malignancy were investigated by MTT, flow cytometry, colony formation experiment, and nude mouse tumor formation experiment. Finally, microarray analysis of TRIP13-related pathways was performed to identify the potential underlying mechanism of TRIP13 in gastric cancer. TRIP13 was found to have high expression in tumor samples. TRIP13 expression status was significantly subjective to tumor-node-metastasis (TNM) staging and poor survival. The downregulation of TRIP13 promoted apoptosis and inhibited tumor growth. TRIP13-dependent JAK/STAT and NF-κB signaling cascade were found as two key pathways in the carcinogenesis of GC. In conclusion, TRIP13 participates in the carcinogenesis of stomach cancer, and its overexpression in the cancerous tissues dovetail with advanced stage and survival. Moreover, TRIP13 functions as an upstream regulator of the JAK/STAT and p53 signaling pathways, which play critical roles in developing various malignancies.

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TRIP 13依赖通路促进胃癌的发展
TRIP13在多种人类肿瘤中高表达,促进肿瘤发生。我们旨在探讨TRIP13对胃癌的生物学作用。从TCGA检索RNA序列数据,评估胃癌组织中TRIP13 mRNA的表达。进一步分析配对的福尔马林固定石蜡包埋块,验证TRIP13表达与致癌状态的关系。通过MTT、流式细胞术、集落形成实验和裸鼠肿瘤形成实验,探讨TRIP13对胃恶性肿瘤增殖的作用。最后,对TRIP13相关通路进行微阵列分析,以确定TRIP13在胃癌中的潜在潜在机制。发现TRIP13在肿瘤样本中有高表达。TRIP13的表达状况与肿瘤淋巴结转移(TNM)分期和生存状况有明显的相关性。下调TRIP13促进细胞凋亡,抑制肿瘤生长。发现依赖于trip13的JAK/STAT和NF-κB信号级联是胃癌发生的两条关键途径。综上所述,TRIP13参与了胃癌的癌变过程,其在癌组织中的过表达与胃癌的晚期及生存期相吻合。此外,TRIP13作为JAK/STAT和p53信号通路的上游调节因子,在各种恶性肿瘤的发生中发挥关键作用。
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来源期刊
CiteScore
3.50
自引率
3.40%
发文量
92
审稿时长
2 months
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?
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