MicroRNA-144 inhibits cell proliferation, migration and invasion in human hepatocellular carcinoma by targeting CCNB1
MicroRNA-144 inhibits cell proliferation, migration and invasion in human hepatocellular carcinoma by targeting CCNB1
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DOI：
10.1186/s12935-019-0729-x
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发表时间：
2019-01-14
影响因子：
5.8
通讯作者：
He, Yuting
中科院分区：
文献类型：
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作者：
Gu, Junsheng;Liu, Xiaorui;He, Yuting
肝细胞癌（Hepatocellular carcinoma，HCC）是世界上最常见的恶性肿瘤之一，发病率和死亡率都很高. MicroRNA是HCC发生的关键调节因子。然而，microRNA在HCC中的调控作用和潜在机制仍然是有限的MethodsCyclin B1（CCNB 1）mRNA水平在非肿瘤和肝癌的癌症基因组图谱（TCGA）队列进行了检查。CCNB 1基因敲减后检测肝癌细胞增殖、迁移和侵袭能力。通过TargetScan分析鉴定靶向CCNB 1的MicroRNA-144，并通过报告基因测定证实。MicroRNA-144的过表达实现了使用microRNA模拟物和microRNA-144的功能进行了测试，在体外肝癌细胞系增殖和体内肿瘤形成experiments.ResultsHere，我们发现，CCNB 1的高水平表达与肝癌患者的预后不良密切相关。RNA干扰技术敲低CCNB 1基因可显著抑制肝癌细胞的增殖、迁移和侵袭。此外，我们发现miR-144直接靶向CCNB 1并抑制CCNB 1的表达。此外，体内皮下成瘤实验进一步证实了miR-144通过负调控CCNB 1延缓肿瘤形成。结论microRNA-144/CCNB 1轴在人肝癌中起重要作用。靶向microRNA-144的治疗可能会改善HCC治疗。
BackgroundHepatocellular carcinoma (HCC) is one of the most common malignancies with a high morbidity and mortality worldwide. MicroRNAs are key regulators of HCC genesis. However, the regulatory role and underlying mechanisms of microRNA in HCC is still limited.MethodsCyclin B1 (CCNB1) mRNA levels were examined in non-tumor and liver cancer of The Cancer Genome Atlas (TCGA) cohort. CCNB1 was knockdown to evaluate the HCC cell proliferation, migration and invasion. MicroRNA-144 targeting CCNB1 was identified with TargetScan analysis and confirmed with reporter assay. Overexpression of MicroRNA-144 was achieved using microRNA mimics and function of microRNA-144 was tested in vitro HCC cell line proliferation and in vivo tumor formation experiments.ResultsHere, we found that the high level expression of CCNB1 was closely associated with poor prognosis in HCC patients. Knockdown of CCNB1 by RNA interference significantly inhibited cell proliferation, migration and invasion in HCC. Furthermore, we found that miR-144 directly targeted CCNB1 and inhibited CCNB1 expression. Moreover, in vivo experiments of subcutaneous tumor formation further demonstrated that miR-144 delayed tumor formation by negative regulation of CCNB1.ConclusionTherefore, we conclude that microRNA-144/CCNB1 axis plays an important role in human HCC. Therapies targeting microRNA-144 could potentially improve HCC treatment.