MicroRNA‑21 regulates the expression of BTG2 in HepG2 liver cancer cells.
MicroRNA‑21 regulates the expression of BTG2 in HepG2 liver cancer cells.
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DOI：
10.3892/mmr.2015.4051
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发表时间：
2015-10
影响因子：
3.4
通讯作者：
Wang G
中科院分区：
文献类型：
--
作者：
Mao B;Xiao H;Zhang Z;Wang D;Wang G
b细胞易位基因2 （BTG2）是一种肿瘤抑制基因，属于抗增殖基因家族。我们前期的研究表明microRNA (miR)-21与BTG2的表达在肝癌发生过程中呈负相关。本研究的目的是探讨miR-21对肝癌细胞生长和进展的影响，并确定其潜在机制。荧光素酶报告基因实验证明BTG2基因是miR-21的直接靶标。此外，采用逆转录-定量聚合酶链反应、western blotting、MTT、流式细胞术、Transwell侵袭试验和伤口愈合试验分析miR-21对HepG2人肝细胞癌（HCC）细胞生长和基因表达的影响。与L02正常肝细胞相比，HepG2细胞中miR-21的表达水平明显升高。BTG2在肝癌细胞系（HepG2和Huh7）中的表达水平明显低于L02细胞。这些结果提示BTG2是miR-21的直接靶基因。在HepG2细胞中，高水平的miR-21抑制BTG2蛋白的表达，抑制miR-21表达则使BTG2蛋白的表达水平升高。抑制miR-21可降低HepG2细胞的增殖和侵袭，增加细胞凋亡率。这些结果表明，miR-21在HepG2细胞中调控细胞增殖、侵袭、迁移和凋亡，这可能与其对BTG2表达的影响有关。本研究结果可能为靶向miR-21/BTG2相互作用治疗HCC提供依据。
B-cell translocation gene 2 (BTG2) is a tumor suppressor gene, which belongs to the anti-proliferation gene family. Our previous study demonstrated that microRNA (miR)-21 and the expression of BTG2 were negatively correlated during hepatocarcinogenesis. The aim of the present study was to investigate the effects of miR-21 on the growth and progression of liver cancer cells, and to determine the underlying mechanism. A luciferase reporter assay was used to demonstrate that the BTG2 gene was a direct target of miR-21. In addition, the effects of miR-21 on cell growth and gene expression in HepG2 human hepatocellular carcinoma (HCC) cells were analyzed using reverse transcription-quantitative polymerase chain reaction, western blotting, an MTT assay, flow cytometry, a Transwell invasion assay and a wound healing assay. The expression levels of miR-21 in the HepG2 cells were significantly higher, compared with those in L02 normal liver cells. The expression levels of BTG2 in liver cancer cell lines (HepG2 and Huh7) were significantly lower, compared with that in the L02 cells. These results suggested that BTG2 was the direct target gene of miR-21. The protein expression levels of BTG2 were inhibited by high expression levels of miR-21, and increased by inhibition of the expression of miR-21 in the HepG2 cells. Inhibition of miR-21 reduced cell proliferation and invasion, and increased the rate of apoptosis in the HepG2 cells. These results indicated that miR-21 regulates cell proliferation, invasion, migration and apoptosis in HepG2 cells, which may be associated with its effects on the expression of BTG2. The results of the present study may provide a basis for targeting the miR-21/BTG2 interaction for the treatment of HCC.