Abstract | BACKGROUND/AIMS: METHODS: qRT-PCR was performed to measure the expression of miRNA and mRNA. Western blot was performed to measure the protein expression. CCK-8 assay was performed to determine cell proliferation. Flow cytometry was performed to detect cell apoptosis. Wounding-healing assay and Transwell assay was performed to detect cell migration and invasion. Dual luciferase reporter assay was performed to verify the target relationship. Quantichrom iron assay was performed to check uptake level of cellular iron. RESULTS: PVT1 expression was up-regulated in HCC tissues and cell lines. Function studies revealed that PVT1 knockdown significantly suppressed cell proliferation, migration and invasion, and induced cell apoptosis in vitro. Furthermore, PVT1 could directly bind to microRNA (miR)-150 and down-regulate miR-150 expression. Hypoxia-inducible protein 2 (HIG2) was found to be one target gene of miR-150, and PVT1 knockdown could inhibit the expression of HIG2 through up-regulating miR-150 expression. In addition, the expression of miR-150 was down-regulated, while the expression of HIG2 was up-regulated in HCC tissues and cell lines. Moreover, inhibition of miR-150 could partly reverse the biological effects of PVT1 knockdown on proliferation, motility, apoptosis and iron metabolism in vitro, which might be associated with dysregulation of HIG2. In vivo results showed that PVT1 knockdown suppressed tumorigenesis and iron metabolism disorder by regulating the expression of miR-150 and HIG2. CONCLUSION: Taken together, the present study demonstrates that PVT1/miR-150/HIG2 axis may lead to a better understanding of HCC pathogenesis and provide potential therapeutic targets for HCC.
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Authors | Yunxiuxiu Xu, Xinxi Luo, Wenguang He, Guangcheng Chen, Yanshan Li, Wenxin Li, Xicheng Wang, Yu Lai, Yibiao Ye |
Journal | Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
(Cell Physiol Biochem)
Vol. 49
Issue 4
Pg. 1403-1419
( 2018)
ISSN: 1421-9778 [Electronic] Germany |
PMID | 30205391
(Publication Type: Journal Article)
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Copyright | © 2018 The Author(s). Published by S. Karger AG, Basel. |
Chemical References |
- Antagomirs
- Cadherins
- HILPDA protein, human
- MIRN150 microRNA, human
- MicroRNAs
- Neoplasm Proteins
- PVT1 long-non-coding RNA, human
- RNA, Long Noncoding
- RNA, Small Interfering
- Vimentin
- Iron
- Vascular Endothelial Growth Factor Receptor-2
- Iron Regulatory Protein 1
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Topics |
- Animals
- Antagomirs
(metabolism)
- Cadherins
(metabolism)
- Carcinoma, Hepatocellular
(drug therapy, metabolism, pathology)
- Cell Line, Tumor
- Cell Movement
- Cell Proliferation
- Humans
- Iron
(metabolism)
- Iron Regulatory Protein 1
(metabolism)
- Liver Neoplasms
(drug therapy, metabolism, pathology)
- Mice
- Mice, Nude
- MicroRNAs
(antagonists & inhibitors, genetics, metabolism)
- Neoplasm Proteins
(antagonists & inhibitors, genetics, metabolism)
- RNA Interference
- RNA, Long Noncoding
(antagonists & inhibitors, genetics, metabolism)
- RNA, Small Interfering
(metabolism, therapeutic use)
- Vascular Endothelial Growth Factor Receptor-2
(metabolism)
- Vimentin
(metabolism)
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