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LncRNAs H19 and HULC, activated by oxidative stress, promote cell migration and invasion in cholangiocarcinoma through a ceRNA manner.
J Hematol Oncol 2016; 9(1):117JH

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.

Authors+Show Affiliations

Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, 510275, People's Republic of China.Department of Hepatobiliary, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China. Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China.Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, 510275, People's Republic of China.Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, 510275, People's Republic of China.Department of Hepatobiliary, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China. Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China.Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, 510275, People's Republic of China.Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, 510275, People's Republic of China. lsscyq@mail.sysu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27809873

Citation

Wang, Wen-Tao, et al. "LncRNAs H19 and HULC, Activated By Oxidative Stress, Promote Cell Migration and Invasion in Cholangiocarcinoma Through a ceRNA Manner." Journal of Hematology & Oncology, vol. 9, no. 1, 2016, p. 117.
Wang WT, Ye H, Wei PP, et al. LncRNAs H19 and HULC, activated by oxidative stress, promote cell migration and invasion in cholangiocarcinoma through a ceRNA manner. J Hematol Oncol. 2016;9(1):117.
Wang, W. T., Ye, H., Wei, P. P., Han, B. W., He, B., Chen, Z. H., & Chen, Y. Q. (2016). LncRNAs H19 and HULC, activated by oxidative stress, promote cell migration and invasion in cholangiocarcinoma through a ceRNA manner. Journal of Hematology & Oncology, 9(1), p. 117.
Wang WT, et al. LncRNAs H19 and HULC, Activated By Oxidative Stress, Promote Cell Migration and Invasion in Cholangiocarcinoma Through a ceRNA Manner. J Hematol Oncol. 2016 11 3;9(1):117. PubMed PMID: 27809873.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - LncRNAs H19 and HULC, activated by oxidative stress, promote cell migration and invasion in cholangiocarcinoma through a ceRNA manner. AU - Wang,Wen-Tao, AU - Ye,Hua, AU - Wei,Pan-Pan, AU - Han,Bo-Wei, AU - He,Bo, AU - Chen,Zhen- Hua, AU - Chen,Yue-Qin, Y1 - 2016/11/03/ PY - 2016/09/15/received PY - 2016/10/18/accepted PY - 2016/11/5/pubmed PY - 2017/12/6/medline PY - 2016/11/5/entrez KW - Cholangiocarcinoma KW - Inflammation response KW - Migration and invasion KW - Oxidative stress KW - ceRNA SP - 117 EP - 117 JF - Journal of hematology & oncology JO - J Hematol Oncol VL - 9 IS - 1 N2 - 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. SN - 1756-8722 UR - https://www.unboundmedicine.com/medline/citation/27809873/LncRNAs_H19_and_HULC_activated_by_oxidative_stress_promote_cell_migration_and_invasion_in_cholangiocarcinoma_through_a_ceRNA_manner_ L2 - https://jhoonline.biomedcentral.com/articles/10.1186/s13045-016-0348-0 DB - PRIME DP - Unbound Medicine ER -