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p53R2 overexpression in cervical cancer promotes AKT signaling and EMT, and is correlated with tumor progression, metastasis and poor prognosis

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机构: [1]Sun Yat Sen Univ, Ctr Canc, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Guangzhou, Guangdong, Peoples R China; [2]Guangzhou Med Univ, Dept Internal Med, Ctr Canc, Guangzhou, Guangdong, Peoples R China; [3]Rutgers State Univ, Robert Wood Johnson Med Sch, Rutgers Canc Inst New Jersey, New Brunswick, NJ USA; [4]Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Pharmacol, New Brunswick, NJ USA; [5]3549 CINJ,195 Little Albany St, New Brunswick, NJ 08903 USA
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关键词: Akt cell growth cervical cancer epithelial-mesenchymal transition p53R2 prognosis

摘要:
p53R2 is a p53-inducible ribonucleotide reductase subunit involved in deoxyribonucleotide biosynthesis and DNA repair. Although p53R2 has been linked to human cancer, its role in cervical cancer remains unknown. In this study, we investigated the expression and clinical significance of p53R2 in early-stage cervical cancer. p53R2 expression is significantly upregulated at both mRNA and protein levels in cervical cancer cells and tissues, compared with that in matched normal cervical cells and tissues, respectively. p53R2 overexpression is associated with increased risk of pelvic lymph node metastasis (PLNM, p = 0.001) and cancer relapse (p = 0.009). Patients with high p53R2 expression have a shorter overall survival (OS) and disease-free survival (DFS). p53R2 is an independent factor for predicting OS and DFS of cervical cancer patients. We further show that p53R2 is important for oncogenic growth, migration and invasion in cervical cancer cells. Mechanistically, p53R2 promotes Akt signaling and epithelial-mesenchymal transition (EMT). In conclusion, our study demonstrates for the first time that p53R2 protein is overexpressed in early-stage cervical cancer and unravels some unconventional oncogenic functions of p53R2. p53R2 may be a useful prognostic biomarker and therapeutic target for cervical cancer.

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出版当年[2017]版:
大类 | 2 区 生物
小类 | 3 区 细胞生物学
最新[2023]版:
大类 | 3 区 生物学
小类 | 4 区 细胞生物学
第一作者:
第一作者机构: [1]Sun Yat Sen Univ, Ctr Canc, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Guangzhou, Guangdong, Peoples R China;
通讯作者:
通讯机构: [1]Sun Yat Sen Univ, Ctr Canc, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Guangzhou, Guangdong, Peoples R China; [3]Rutgers State Univ, Robert Wood Johnson Med Sch, Rutgers Canc Inst New Jersey, New Brunswick, NJ USA; [4]Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Pharmacol, New Brunswick, NJ USA; [5]3549 CINJ,195 Little Albany St, New Brunswick, NJ 08903 USA
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