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

The 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. In situ hybridization (ISH) and quantitative real-time PCR (qPCR) were performed to detect the ex...

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Bibliographic Details
Published in:Molecular cancer Vol. 18; no. 1; pp. 33 - 16
Main Authors: Chen, Jianan, Yu, Yan, Li, Hua, Hu, Qiuyue, Chen, Xiaolong, He, Yuting, Xue, Chen, Ren, Fang, Ren, Zhigang, Li, Juan, Liu, Liwen, Duan, Zhenfeng, Cui, Guangying, Sun, Ranran
Format: Journal Article
Language:English
Published: England BioMed Central Ltd 02.03.2019
Springer Nature B.V
BioMed Central
BMC
Subjects:
Adolescent
Adult
Animals
Biotin
Cancer
Cancer metastasis
Carcinoma - genetics
Carcinoma - metabolism
Carcinoma - mortality
Carcinoma - pathology
Cell growth
Cell Line, Tumor
Cell lines
Cell migration
Cell Movement
Cell Proliferation
Cell survival
Cholecystokinin
Development and progression
Diagnosis
Female
Gallbladder
Gallbladder cancer
Gallbladder Neoplasms - genetics
Gallbladder Neoplasms - metabolism
Gallbladder Neoplasms - mortality
Gallbladder Neoplasms - pathology
Gastric cancer
Gene expression
Gene Expression Regulation, Neoplastic
Genetic aspects
Glucose
Glucose - metabolism
Glycolysis - genetics
Hexokinase
Hexokinase - genetics
Hexokinase - metabolism
HK2
Humans
Hybridization
Immunohistochemistry
Immunoprecipitation
Journalists
Liver cancer
Long non-coding RNA
Luciferase
Lymphatic Metastasis
Male
Medical prognosis
Metabolism
Metastases
Metastasis
Mice
MicroRNA
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
Middle Aged
miR-143
Neoplasm Staging
Non-coding RNA
Novels
Prostate cancer
PVT1
RNA
RNA, Long Noncoding - antagonists & inhibitors
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
RNA, Small Interfering - genetics
RNA, Small Interfering - metabolism
Signal Transduction
Studies
Survival Analysis
Therapeutic applications
Tumorigenesis
Tumors
Wound care
Wound healing
Xenograft Model Antitumor Assays
Xenografts
China
miR-143
PVT1
Gallbladder cancer
HK2
Long non-coding RNA
ISSN:1476-4598, 1476-4598
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Summary:The 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. In 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. PVT1 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. The 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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ISSN:1476-4598
1476-4598
DOI:10.1186/s12943-019-0947-9