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Molecular Cancer
Published in: Molecular Cancer 1/2019

Open Access 01-12-2019 | Gallbladder Cancer | Research

LncRNA-HGBC stabilized by HuR promotes gallbladder cancer progression by regulating miR-502-3p/SET/AKT axis

Authors: Yun-ping Hu, Yun-peng Jin, Xiang-song Wu, Yang Yang, Yong-sheng Li, Huai-feng Li, Shan-shan Xiang, Xiao-ling Song, Lin Jiang, Yi-jian Zhang, Wen Huang, Shi-li Chen, Fa-tao Liu, Chen Chen, Qin Zhu, Hong-zhuan Chen, Rong Shao, Ying-bin Liu

Published in: Molecular Cancer | Issue 1/2019

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Abstract

Backgrounds

Long non-coding RNAs (lncRNAs) are essential factors that regulate tumor development and metastasis via diverse molecular mechanisms in a broad type of cancers. However, the pathological roles of lncRNAs in gallbladder carcinoma (GBC) remain largely unknown. Here we discovered a novel lncRNA termed lncRNA Highly expressed in GBC (lncRNA-HGBC) which was upregulated in GBC tissue and aimed to investigate its role and regulatory mechanism in the development and progression of GBC.

Methods

The expression level of lncRNA-HGBC in GBC tissue and different cell lines was determined by quantitative real-time PCR. The full length of lncRNA-HGBC was obtained by 5′ and 3′ rapid amplification of the cDNA ends (RACE). Cellular localization of lncRNA-HGBC was detected by fluorescence in situ hybridization (FISH) assays and subcellular fractionation assay. In vitro and in vivo assays were preformed to explore the biological effects of lncRNA-HGBC in GBC cells. RNA pull-down assay, mass spectrometry, and RNA immunoprecipitation (RIP) assay were used to identify lncRNA-HGBC-interacting proteins. Dual luciferase reporter assays, AGO2-RIP, and MS2-RIP assays were performed to verify the interaction between lncRNA-HGBC and miR-502-3p.

Results

We found that lncRNA-HGBC was upregulated in GBC and its upregulation could predict poor survival. Overexpression or knockdown of lncRNA-HGBC in GBC cell lines resulted in increased or decreased, respectively, cell proliferation and invasion in vitro and in xenografted tumors. LncRNA-HGBC specifically bound to RNA binding protein Hu Antigen R (HuR) that in turn stabilized lncRNA-HGBC. LncRNA-HGBC functioned as a competitive endogenous RNA to bind to miR-502-3p that inhibits target gene SET. Overexpression, knockdown or mutation of lncRNA-HGBC altered the inhibitory effects of miR-502-3p on SET expression and downstream activation of AKT. Clinically, lncRNA-HGBC expression was negatively correlated with miR-502-3p, but positively correlated with SET and HuR in GBC tissue.

Conclusions

Our study demonstrates that lncRNA-HGBC promotes GBC metastasis via activation of the miR-502-3p-SET-AKT cascade, pointing to lncRNA-HGBC as a new prognostic predictor and a therapeutic target.
Appendix
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Metadata
Title
LncRNA-HGBC stabilized by HuR promotes gallbladder cancer progression by regulating miR-502-3p/SET/AKT axis
Authors
Yun-ping Hu
Yun-peng Jin
Xiang-song Wu
Yang Yang
Yong-sheng Li
Huai-feng Li
Shan-shan Xiang
Xiao-ling Song
Lin Jiang
Yi-jian Zhang
Wen Huang
Shi-li Chen
Fa-tao Liu
Chen Chen
Qin Zhu
Hong-zhuan Chen
Rong Shao
Ying-bin Liu
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2019
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-019-1097-9

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