胰岛素样生长因子 2 mRNA 结合蛋白 2 是卵巢癌的治疗靶点。

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2023-12-01 Epub Date: 2023-12-12 DOI:10.1177/15353702231214268
Jia Yuan, Xin Li, Fanchen Wang, Huiqiang Liu, Wencai Guan, Guoxiong Xu
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引用次数: 0

摘要

卵巢癌(OC)是一种致命的妇科疾病。卵巢癌患者最常见的治疗方法是手术联合化疗,但大多数晚期患者最终会因化疗耐药而复发。本研究探讨了胰岛素样生长因子2 mRNA结合蛋白2(IGF2BP2)在OC中的作用和功能。我们采用实时定量聚合酶链反应(qRT-PCR)和免疫印迹法分别观察到 IGF2BP2 mRNA 和蛋白在 OC 细胞和组织中的表达上调。癌症基因组图谱(The Cancer Genome Atlas,TCGA)和临床肿瘤蛋白质组分析联盟(Clinical Proteomic Tumor Analysis Consortium,CPTAC)的分析分别验证了IGF2BP2在mRNA和蛋白质水平上的表达增加。基因表达总库(GEO)和癌症细胞系百科全书(CCLE)数据库用于分析 IGF2BP2 的表达和临床价值。基因组富集分析(GSEA)、京都基因与基因组百科全书(KEGG)和基因本体论(GO)分析探讨了IGF2BP2的生物学功能和参与细胞生长的情况。事实上,通过细胞计数试剂盒-8(Cell Counting Kit-8)测定,敲除 IGF2BP2 可抑制 OC 细胞的增殖。IGF2BP2 基因组扩增是其过度表达的部分原因。IGF2BP2的高表达与信号转导和激活转录1(STAT1)和药物敏感性有关,并与OC患者的不良生存结果相关。此外,研究人员还分别使用 "pRRophetic "R软件包和癌症免疫图谱(TCIA)数据库分析了化疗和免疫疗法的反应性。IGF2BP2的低表达与化疗耐药有关,但与高肿瘤微环境评分和肿瘤浸润免疫细胞有关,这表明免疫疗法可能适用于化疗耐药患者。IGF2BP2 表达的改变可能会对化疗和免疫疗法产生反应。因此,IGF2BP2有望成为OC的治疗靶点和诊断生物标志物。
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Insulin-like growth factor 2 mRNA-binding protein 2 is a therapeutic target in ovarian cancer.

Ovarian cancer (OC) is a fatal gynecologic disease. The most common treatment for OC patients is surgery combined with chemotherapy but most patients at advanced stages eventually develop relapse due to chemoresistance. This study examined the role and function of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) in OC. We observed that the expression of IGF2BP2 mRNA and protein was up-regulated in OC cells and tissues using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. An increase in IGF2BP2 expression at mRNA and protein levels was verified by the analyses of The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC), respectively. Gene Expression Omnibus (GEO) and Cancer Cell Line Encyclopedia (CCLE) databases were applied to analyze the expression and clinical value of IGF2BP2. Gene set enrichment analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) analyses explored biological functions and the involvement of IGF2BP2 in cell growth. Indeed, the knockdown of IGF2BP2 resulted in the inhibition of OC cell proliferation evaluated by the Cell Counting Kit-8 assay. Genomic amplification of IGF2BP2 partly accounted for its overexpression. High expression of IGF2BP2 was associated with signal transducer and activator of transcription 1 (STAT1) and drug sensitivity and was correlated with an unfavorable survival outcome in OC patients. Furthermore, the responsiveness of chemotherapy and immunotherapy were analyzed using the "pRRophetic" R package and The Cancer Immune Atlas (TCIA) database, respectively. The low expression of IGF2BP2 was associated with chemoresistance but with high tumor microenvironment scores and tumor-infiltrating immune cells, suggesting that immunotherapy may apply in chemoresistant patients. The alteration of IGF2BP2 expression may respond to chemotherapy and immunotherapy. Thus, IGF2BP2 shows potential as a therapeutic target and diagnostic biomarker for OC.

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ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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