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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2016

Open Access 01-12-2016 | Research

LncRNAs H19 and HULC, activated by oxidative stress, promote cell migration and invasion in cholangiocarcinoma through a ceRNA manner

Authors: Wen-Tao Wang, Hua Ye, Pan-Pan Wei, Bo-Wei Han, Bo He, Zhen- Hua Chen, Yue-Qin Chen

Published in: Journal of Hematology & Oncology | Issue 1/2016

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Abstract

Background

Long non-coding RNAs (lncRNAs) are known to play important roles in different cell contexts, including cancers. However, little is known about lncRNAs in cholangiocarcinoma (CCA), a cholangiocyte malignancy with poor prognosis, associated with chronic inflammation and damage to the biliary epithelium. The aim of the study is to identify if any lncRNA might associate with inflammation or oxidative stress in CCA and regulate the disease progression.

Methods

In this study, RNA-seqs datasets were used to identify aberrantly expressed lncRNAs. Small interfering RNA and overexpressed plasmids were used to modulate the expression of lncRNAs, and luciferase target assay RNA immunoprecipitation (RIP) was performed to explore the mechanism of miRNA-lncRNA sponging.

Results

We firstly analyzed five available RNA-seqs datasets to investigate aberrantly expressed lncRNAs which might associate with inflammation or oxidative stress. We identified that two lncRNAs, H19 and HULC, were differentially expressed among all the samples under the treatment of hypoxic or inflammatory factors, and they were shown to be stimulated by short-term oxidative stress responses to H2O2 and glucose oxidase in CCA cell lines. Further studies revealed that these two lncRNAs promoted cholangiocyte migration and invasion via the inflammation pathway. H19 and HULC functioned as competing endogenous RNAs (ceRNAs) by sponging let-7a/let-7b and miR-372/miR-373, respectively, which activate pivotal inflammation cytokine IL-6 and chemokine receptor CXCR4.

Conclusions

Our study revealed that H19 and HULC, up-regulated by oxidative stress, regulate CCA cell migration and invasion by targeting IL-6 and CXCR4 via ceRNA patterns of sponging let-7a/let-7b and miR-372/miR-373, respectively. The results suggest that these lncRNAs might be the chief culprits of CCA pathogenesis and progression. The study provides new insight into the mechanism linking lncRNA function with CCA and may serve as novel targets for the development of new countermeasures of CCA.
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Metadata
Title
LncRNAs H19 and HULC, activated by oxidative stress, promote cell migration and invasion in cholangiocarcinoma through a ceRNA manner
Authors
Wen-Tao Wang
Hua Ye
Pan-Pan Wei
Bo-Wei Han
Bo He
Zhen- Hua Chen
Yue-Qin Chen
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2016
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-016-0348-0

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