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Transcription factor HIF1α promotes proliferation, migration, and invasion of cholangiocarcinoma via long noncoding RNA H19/microRNA-612/Bcl-2 axis.
Metadata
Journaltranslational research5.411Date
2020 Jun 04
4 months ago
Type
Journal Article
Volume
2020-10 / 224 : 26-39
Author
Yu A 1, Zhao L 2, Kang Q 3, Li J 3, Chen K 3, Fu H 3
Affiliation
  • 2. The First Department of Gynecology, Affiliated Hospital of Chengde Medical University, Chengde, P.R. China.
  • 3. The First Department of General Surgery, Affiliated Hospital of Chengde Medical University, Chengde, P.R. China.
Doi
PMIDMESH
Adult
Aged
Animals
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cholangiocarcinoma
Down-Regulation
Female
Gene Expression Regulation, Neoplastic
Gene Silencing
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
Male
Mice, Nude
MicroRNAs
Middle Aged
Models, Biological
Neoplasm Invasiveness
Proto-Oncogene Proteins c-bcl-2
RNA, Long Noncoding
Signal Transduction
Xenograft Model Antitumor Assays
Abstract
Cholangiocarcinoma, which is the most common invasive malignant tumor of the biliary tract, has poor prognosis. There is evidence suggesting that hypoxia-inducible factor 1α (HIF1α) plays an important role in cholangiocarcinoma. Also, microRNA-612 (miR-612) is another key regulator of cholangiocarcinoma. In this study, we investigate the scantly documented interaction of HIF1α and miR-612 in cholangiocarcinoma. We first undertook microarray-based cholangiocarcinoma gene expression profiles to screen out the differentially expressed long noncoding RNAs (lncRNAs) and genes. We used reverse transcription quantitative polymerase chain reaction to detect the expression of HIF1α in normal bile duct and cholangiocarcinoma tissues, and in corresponding cells lines. Cell counting kit 8, scratch, and Transwell assays were used to detect the proliferation, migration and invasion of cholangiocarcinoma cells. Cell cycle distribution and apoptosis were detected by flow cytometry. ChIP, dual luciferase reporter gene assay, RNA pull-down, and RNA immunoprecipitation were used to verify relationship between HIF1α and lncRNA H19, and lncRNA H19 and miR-612. We also monitored tumor formation in nude mice to verify the effect of HIF1α on cholangiocarcinoma. HIF1α expression was elevated in cholangiocarcinoma tissues and cells. Silencing HIF1α reduced proliferation, migration, and invasion of cholangiocarcinoma cells. HIF1α transcriptionally activated the expression of lncRNA H19. Overexpression of miR-612 could rescue the proliferation, migration and invasion of cholangiocarcinoma cells caused by lncRNA H19 overexpression. Taken together, HIF1α activated lncRNA H19-mediated miR-612/Bcl-2 pathway to promote cholangiocarcinoma, suggesting a promising therapeutic target for cholangiocarcinoma.
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5.4
Transl Restranslational research
Metadata
LocationUnited States
FromELSEVIER SCIENCE INC

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