Insulin-like growth factor 2 mRNA-binding protein 2 is a therapeutic target in ovarian cancer

被引:2
|
作者
Yuan, Jia [1 ,2 ]
Li, Xin [1 ,2 ]
Wang, Fanchen [1 ,2 ]
Liu, Huiqiang [1 ,2 ]
Guan, Wencai [1 ]
Xu, Guoxiong [1 ,2 ,3 ]
机构
[1] Fudan Univ, Jinshan Hosp, Res Ctr Clin Med, 1508 Longhang Rd, Shanghai 201508, Peoples R China
[2] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China
[3] Fudan Univ, Jinshan Hosp, Ctr Tumor Diag & Therapy, Shanghai 201508, Peoples R China
基金
中国国家自然科学基金;
关键词
Chemotherapy; drug resistance; immune; ovarian tumor; prognosis; STAT1; COMBINATION THERAPY; OVEREXPRESSION; EXPRESSION; SURVIVAL; PLATINUM; CTLA-4;
D O I
10.1177/15353702231214268
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:2198 / 2209
页数:12
相关论文
共 50 条
  • [1] The Roles of Insulin-Like Growth Factor 2 mRNA-Binding Protein 2 in Cancer and Cancer Stem Cells
    Cao, Junguo
    Mu, Qingchun
    Huang, Haiyan
    STEM CELLS INTERNATIONAL, 2018, 2018
  • [2] Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in cancer
    Huang, Xinwei
    Zhang, Hong
    Guo, Xiaoran
    Zhu, Zongxin
    Cai, Haibo
    Kong, Xiangyang
    JOURNAL OF HEMATOLOGY & ONCOLOGY, 2018, 11
  • [3] Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in cancer
    Xinwei Huang
    Hong Zhang
    Xiaoran Guo
    Zongxin Zhu
    Haibo Cai
    Xiangyang Kong
    Journal of Hematology & Oncology, 11
  • [4] The RNA-binding protein insulin-like growth factor 2 mRNA-binding protein 3 is oncogenic in liposarcoma
    Angeles, Christina V.
    Hefner, Markus
    Socci, Nicholas D.
    DeCarolis, Penelope
    Tuschl, Thomas
    Singer, Samuel
    CANCER RESEARCH, 2010, 70
  • [5] The Oncogenic Functions of Insulin-like Growth Factor 2 mRNA-Binding Protein 3 in Human Carcinomas
    Wang, Peng-Fei
    Wang, Xiaoyu
    Liu, Min
    Zeng, Zheng
    Lin, Caiji
    Xu, Wenwen
    Ma, Wenqing
    Wang, Jiali
    Xiang, Qian
    Johnston, Randal N.
    Liu, Huidi
    Liu, Shu-Lin
    CURRENT PHARMACEUTICAL DESIGN, 2020, 26 (32) : 3939 - 3954
  • [6] Identification of insulin-like growth factor 2 mRNA-binding protein 3 as a radioresistance factor in squamous esophageal cancer cells
    Yoshino, K.
    Motoyama, S.
    Koyota, S.
    Shibuya, K.
    Sato, Y.
    Sasaki, T.
    Wakita, A.
    Saito, H.
    Minamiya, Y.
    Sugiyama, T.
    Ogawa, J.
    DISEASES OF THE ESOPHAGUS, 2014, 27 (05) : 479 - 484
  • [7] Inhibition of insulin-like growth factor 2 mRNA-binding protein 1 sensitizes colorectal cancer cells to chemotherapeutics
    Betson, Nicole
    Hajahmed, Mohammed
    Gebretsadek, Tsige
    Ndebele, Kenneth
    Ahmad, H. Anwar
    Tchounwou, Paul B.
    Spiegelman, Vladimir S.
    Noubissi, Felicite K.
    FASEB BIOADVANCES, 2022, 4 (12) : 816 - 829
  • [8] Insulin-like Growth Factor 2 mRNA-Binding Protein 2-a Potential Link Between Type 2 Diabetes Mellitus and Cancer
    Cao, Junguo
    Yan, Weijia
    Ma, Xiujian
    Huang, Haiyan
    Yan, Hong
    JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2021, 106 (10): : 2807 - 2818
  • [9] Targeting insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) for the treatment of cancer
    Cai, Yuanqian
    Wang, Yingzhe
    Mao, Bingjie
    You, Qidong
    Guo, Xiaoke
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2024, 268
  • [10] Role of insulin-like growth factor 2 mRNA-binding protein 1 in basal cell carcinoma development
    Noubissi, F.
    Harris, C.
    Hajahmed, M.
    Yedjou, C.
    JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2022, 142 (08) : S16 - S16