IGF2BP3 promotes cell metastasis and is associated with poor patient survival in nasopharyngeal carcinoma

被引:17
|
作者
Xu, Yun [1 ,2 ,3 ]
Guo, Zhoubo [1 ,2 ]
Peng, Hewei [4 ]
Guo, Lanyan [5 ]
Wang, Ping [1 ,2 ]
机构
[1] Tianjin Med Univ, Canc Inst & Hosp, Natl Clin Res Ctr Canc,Dept Radiat, Key Lab Canc Prevent & Therapy,Tianjins Clin Res, Tianjin, Peoples R China
[2] Tianjin Med Univ, Canc Inst & Hosp, Natl Clin Res Ctr Canc,Dept Oncol, Key Lab Canc Prevent & Therapy,Tianjins Clin Res, Tianjin, Peoples R China
[3] Fujian Med Univ, Canc Hosp, Fujian Canc Hosp, Fujian, Peoples R China
[4] Fujian Med Univ, Dept Epidemiol & Hlth Stat, Fujian Prov Key Lab Environm Factors & Canc, Sch Publ Hlth, Fuzhou, Peoples R China
[5] Fujian Med Univ, Sch Med Technol & Engn, Fuzhou, Peoples R China
关键词
IGF2BP3; Metastasis; mTOR; Nasopharyngeal carcinoma; RNA-BINDING PROTEIN-3; INSULIN; EXPRESSION; MARKER;
D O I
10.1111/jcmm.17093
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Metastasis contributes to treatment failure in nasopharyngeal carcinoma (NPC) patients. Our study aimed at elucidating the role of insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) in NPC metastasis and the underlying mechanism involved. IGF2BP3 expression in NPC was determined by bioinformatics, quantitative polymerase chain reaction and immunohistochemistry analyses. The biological function of IGF2BP3 was investigated by using in vitro and in vivo studies. In this study, IGF2BP3 mRNA and protein levels were elevated in NPC tissues. In addition, IGF2BP3 exerted an oncogenic role by promoting epithelial-mesenchymal transition (EMT), thereby inducing NPC cell migration and invasion. Further studies revealed that IGF2BP3 regulated the expression of key regulators of EMT by activating AKT/mTOR signalling, thus stimulating NPC cell migration and invasion. Remarkably, targeting IGF2BP3 delayed NPC metastasis through attenuating p-AKT and vimentin expression and inducing E-cadherin expression in vivo. Moreover, IGF2BP3 protein levels positively correlated with distant metastasis after initial treatment. Importantly, IGF2BP3 expression served as an independent prognostic factor in predicting the overall survival and distant metastasis-free survival of NPC patients. This work identifies IGF2BP3 as a novel prognostic marker and a new target for NPC treatment.
引用
收藏
页码:410 / 421
页数:12
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