HnRNPR-CCNB1/CENPF axis contributes to gastric cancer proliferation and metastasis

被引:108
作者
Chen, Er-Bao [1 ]
Qin, Xuan [2 ]
Peng, Ke [1 ]
Li, Qian [1 ]
Tang, Cheng [1 ]
Wei, Yi-Chou [1 ]
Yu, Shan [1 ]
Gan, Lu [1 ]
Liu, Tian-Shu [1 ,3 ]
机构
[1] Fudan Univ, Zhongshan Hosp, Dept Med Oncol, Shanghai, Peoples R China
[2] Peking Univ, Sch Chem Biol & Biotechnol, Shenzhen Grad Sch, Shenzhen, Peoples R China
[3] Fudan Univ, Ctr Evidence Based Med, Shanghai, Peoples R China
来源
AGING-US | 2019年 / 11卷 / 18期
基金
中国国家自然科学基金;
关键词
hnRNPR; gastric cancer; RNA binding protein; CCNB1; CENPF; CENTROMERE PROTEIN F; CYCLIN B1 EXPRESSION; RNA-BINDING PROTEINS; SURVIVAL; PROGRESSION; PROGNOSIS; CELLS; MIRNA;
D O I
10.18632/aging.102254
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Gastric cancer (GC) is a common disease globally with high mortality rate. It is therefore necessary to develop novel therapies targeting specific events in the pathogenesis of GC. Some hnRNP family members are involved in multiple cancer biological behaviors. However, the potential function and mechanism of hnRNPR, a new molecule of hnRNP family in GC remains unknown. We found that the expression of hnRNPR was significantly overexpressed in multiple cancers compared to the normal tissues. Functionally, hnRNPR promoted cancer cell proliferation, migration, and invasion. Knockdown of hnRNPR in two type mice models, with two types of tumors models decreased the tumor aggressiveness and metastasis. Mechanistically, hnRNPR targeted oncogenic pathways by stabilizing the expression of CCNB1 and CENPF mRNA level. Knockdown of CCNB1 and CENPF abolished the hnRNPR-induced cell growth and invasion, respectively. Furthermore, the protein level of hnRNPR in the tumor was positively correlated with the expression of CCNB1 and CENPF in clinical samples. Together, these results indicate that overexpression of hnRNPR promoted the aggressiveness of GC by increasing the mRNA expression of CCNB1 and CENPF. HnRNPR-CCNB1/CENPF axis may be a potential therapeutic target for GC treatment.
引用
收藏
页码:7473 / 7491
页数:19
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