miR-125b-5p inhibits cell proliferation, migration, and invasion in hepatocellular carcinoma via targeting TXNRD1
miR-125b-5p inhibits cell proliferation, migration, and invasion in hepatocellular carcinoma via targeting TXNRD1
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miR-125b-5p 通过靶向 TXNRD1 抑制肝细胞癌细胞增殖、迁移和侵袭
DOI：
10.1186/s12935-019-0919-6
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发表时间：
2019-07-30
影响因子：
5.8
通讯作者：
Lu, Ligong
中科院分区：
文献类型：
--
作者：
Hua, Shengni;Quan, Yingyao;Lu, Ligong
研究背景硫氧还蛋白还原酶1（TXNRD 1）是一种抗氧化酶，在肝细胞癌（HCC）中表达过强，但其在HCC中的具体功能和机制尚不清楚。方法采用定量逆转录聚合酶链反应（qRT-PCR）检测人肝癌组织中miR-125 b-5 p的表达水平，并通过体外实验研究miR-125 b-5 p对肝癌细胞增殖、迁移和侵袭的影响。此外，我们还通过qRT-PCR和western blotting检测了miR-125 b-5 p对TXNRD 1表达的影响，并通过双链转移酶-报告基因分析证实miR-125 b-5 p直接靶向TXNRD 1 mRNA的3′非翻译区。这一发现在来自基因表达综合数据库和癌症基因组图谱的HCC群组中得到证实。此外，低miR-125 b-5 p表达与HCC患者的不良预后相关，基因集富集分析表明miR-125 b-5 p水平与HCC增殖和转移相关。如预测的那样，过表达miR-125 b-5 p抑制Huh 7和SK-Hep-1细胞的增殖、迁移和侵袭，并迫使miR-125 b-5 p下调HCC细胞中TXNRD 1 mRNA和蛋白水平的表达。此外，双酶-报告基因分析显示，miR-125 b-5 p靶向TXNRD 1直接调控其表达，而TXNRD 1过表达则可消除miR-125 b-5 p对HCC细胞增殖、迁移和侵袭的抑制作用，提示miR-125 b-5 p通过抑制TXNRD 1在HCC中发挥抑癌作用，可作为HCC临床治疗的潜在靶点。
BackgroundThioredoxin reductase 1(TXNRD1) is an antioxidant enzyme reportedly overexpressed in hepatocellular carcinoma (HCC); however, the detailed function and mechanisms of TXNRD1 in HCC remain obscure. In this study, we investigated the miR-125b-5p-specific regulation ofTXNRD1levels and its effect on HCC cells.MethodsWe detected miR-125b-5p levels in human HCC tissue samples through quantitative reverse transcription polymerase chain reaction (qRT-PCR), and in vitro experiments were employed to investigate the effect of miR-125b-5p on HCC cell proliferation, migration, and invasion. Additionally, we examined miR-125b-5p-mediated changes in TXNRD1 levels by qRT-PCR and western blotting, and a dual luciferase-reporter assay was conducted to confirm direct targeting of the 3′ untranslated region of TXNRD1 mRNA by miR-125b-5p.ResultsmiR-125b-5p expression was reduced in HCC tissues relative to that in matched para-carcinoma tissues; this finding was verified in HCC cohorts from the Gene Expression Omnibus and The Cancer Genome Atlas. Additionally, low miR-125b-5p expression was associated with poor prognosis in HCC patients, and gene-set enrichment analysis indicated that miR-125b-5p levels were associated with HCC proliferation and metastasis. As predicted, overexpressing miR-125b-5p restrained the proliferation, migration, and invasion of Huh7 and SK-Hep-1 cells and forced expression of the miR-125b-5p-downregulated TXNRD1 mRNA and protein levels in HCC cells. Moreover, dual luciferase-reporter assays revealed that miR-125b-5p targetsTXNRD1to directly regulate its expression, whereasTXNRD1overexpression abolishes the inhibitory effect of miR-125b-5p on HCC cell proliferation, migration, and invasion.ConclusionsThese results demonstrated miR-125b-5p as a tumor suppressor in HCC through its inhibition ofTXNRD1, thereby suggesting it as a potential target for the clinical treatment of HCC.