microRNA-218 suppresses the proliferation, invasion and promotes apoptosis of pancreatic cancer cells by targeting HMGB1
查看参考文献57篇
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文摘
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Objective: To detect the expression profiles of microRNA-218 (miR-218) in human pancreatic cancer tissue (PCT) and cells and their effects on the biological features of human pancreatic cancer cell line PANC-1 and observe the effect of miR-218 on the expression of the target gene high mobility group box 1 (HMGB1), with an attempt to provide new treatment methods and strategies for pancreatic cancer. Methods: The expressions of miR-218 in PCT and normal pancreas tissue as well as in various pancreatic cancer cell lines including AsPC-1, BxPC-3, and PANC-1 were determined with quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The change of miR-218 expression in PANC-1 cells was detected using qRT-PCT after the transfection of miR-218 mimic for 48 h. Cell Counting Kit-8 (CCK-8) was applied for detecting the effect of miR-218 on the activity of PANC-1 cells. The effects of miR-218 on the proliferation and apoptosis of PANC-1 cells were analyzed using the flow cytometry. The effect of miR-218 on the migration of PANC-1 cells was detected using the Trans-well migration assay. The HMGB1 was found to be a target gene of miR-218 by luciferase reporter assay, and the effect of miR-218 on the expression of HMGB1 protein in cells were determined using Western blotting. Results: As shown by qRT-PCR, the expressions of miR-218 in PCT and in pancreatic cancer cell line significantly decreased when compared with the normal pancreatic tissue (NPT) (P<0.01). Compared with the control group, the miR-218 expression significantly increased in the PANC-1 group after the transfection of miR-218 mimic for 48 h (P<0.01). Growth curve showed that the cell viability significantly dropped after the overexpression of miR-218 in the PANC-1 cells for two days (P<0.05). Flow cytometry showed that the S-phase fraction significantly dropped after the overexpression of miR-218 (P<0.01) and the percentage of apoptotic cells significantly increased (P<0.01). As shown by the Trans-well migration assay, the enhanced miR-218 expression was associated with a significantly lower number of cells that passed through a Transwell chamber (P<0.01). Luciferase reporter assay showed that, compared with the control group, the relative luciferase activity significantly decreased in the miR-218 mimic group (P<0.01). As shown by the Western blotting, compared with the control group, the HMGB1 protein expression significantly decreased in the PANC-1 group after the transfection of miR-218 mimic for 48 h (P<0.01). Conclusions: The miR-218 expression decreases in human PCT and cell lines. miR-218 can negatively regulate the HMGB1 protein expression and inhibit the proliferation and invasion of pancreatic cancer cells. A treatment strategy by enhancing the miR-218 expression may benefit the patients with pancreatic cancer. |
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来源
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Chinese Journal of Cancer Research
,2015,27(3):247-257 【核心库】
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DOI
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10.3978/j.issn.1000-9604.2015.04.07
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关键词
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Pancreatic cancer
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microRNA-218 (miR-218)
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proliferation
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apoptosis
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high mobility group box 1 (HMGB1)
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地址
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1.
Department of Pancreatic Surgery, First Hospital of China Medical University, Shenyang, 110000
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Department of Otorhinolaryngolc Fengtian Hospital, Shenyang Medical University, Shenyang, 110024
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语种
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英文 |
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文献类型
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研究性论文 |
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ISSN
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1000-9604 |
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学科
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生物化学 |
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基金
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(III) The Shenyang Municipal Science and Technology Project
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(II) Liaoning Province Science and Technology Plan Project
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supported by grants: (I) Liaoning Provincial Department of Education Science Research Project
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文献收藏号
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CSCD:5467264
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