Long non-coding RNA PVT1 promotes tumor progression by regulating the miR-143/HK2 axis in gallbladder cancer

被引:312
作者
Chen, Jianan [1 ,2 ]
Yu, Yan [1 ,2 ]
Li, Hua [1 ,2 ]
Hu, Qiuyue [1 ,2 ]
Chen, Xiaolong [1 ,2 ]
He, Yuting [1 ,2 ]
Xue, Chen [1 ,2 ]
Ren, Fang [2 ]
Ren, Zhigang [1 ,2 ]
Li, Juan [1 ,2 ]
Liu, Liwen [1 ,2 ]
Duan, Zhenfeng [3 ]
Cui, Guangying [1 ,2 ]
Sun, Ranran [1 ,2 ,4 ]
机构
[1] Zhengzhou Univ, Affiliated Hosp 1, Precis Med Ctr, Zhengzhou 450052, Henan, Peoples R China
[2] Zhengzhou Univ, Affiliated Hosp 1, Key Lab Clin Med, Zhengzhou 450052, Henan, Peoples R China
[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Orthopaed Surg, Sarcoma Biol Lab, Angeles, CA 90095 USA
[4] Zhengzhou Univ, Affiliated Hosp 1, Natl Engn Lab Internet Med Syst & Applicat, Zhengzhou 450052, Henan, Peoples R China
基金
中国国家自然科学基金;
关键词
Long non-coding RNA; PVT1; HK2; miR-143; Gallbladder cancer; TARGETING HEXOKINASE 2; POOR-PROGNOSIS; CELL-PROLIFERATION; SUPPRESSOR; ACTS;
D O I
10.1186/s12943-019-0947-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
BackgroundThe long non-coding RNA PVT1 (lncRNA PVT1) has been reported to act as an oncogenic regulator of several cancers. However, its expression and function in gallbladder cancer (GBC) remain largely unknown.MethodsIn situ hybridization (ISH) and quantitative real-time PCR (qPCR) were performed to detect the expression of PVT1 and miR-143 in GBC tissues and cell lines. Immunohistochemistry (IHC) assays were performed to assess the expression of the hexokinase 2 (HK2) protein. The relationships among PVT1, miR-143 and HK2 were evaluated using dual-luciferase reporter, RNA immunoprecipitation (RIP) and biotin pull-down assays. The biological functions of PVT1, miR-143 and HK2 in GBC cells were explored with cell counting kit 8 (CCK-8), 5-ethynyl-20-deoxyuridine (EdU), colony formation, transwell, wound healing and glucose metabolism assays in vitro. For in vivo experiments, a xenograft model was used to investigate the effects of PVT1 and HK2 on GBC.ResultsPVT1 was upregulated in GBC tissues and cells and was positively associated with malignancies and worse overall survival. PVT1 knockdown inhibited cell proliferation, migration, and invasion in vitro and restrained tumor growth in vivo. Further studies demonstrated that PVT1 positively regulated HK2 expression via its competing endogenous RNA (ceRNA) activity on miR-143. Additionally, HK2 expression and function were positively correlated with PVT1. Furthermore, we observed that the PVT1/miR-143/HK2 axis promoted cell proliferation and metastasis by regulating aerobic glucose metabolism in GBC cells.ConclusionsThe results of our study reveal a potential ceRNA regulatory pathway in which PVT1 modulates HK2 expression by competitively binding to endogenous miR-143 in GBC cells, which may provide new insights into novel molecular therapeutic targets for GBC.
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页数:16
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