MiR-138 induces cell cycle arrest by targeting cyclin D3 in hepatocellular carcinoma.

MiR-138 induces cell cycle arrest by targeting cyclin D3 in hepatocellular carcinoma.
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DOI:
10.1093/carcin/bgs113
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发表时间:
2012-05
期刊:
影响因子:
4.7
通讯作者:
Qi ZT
Qi ZT
中科院分区:
医学2区
文献类型:
--
作者:
Wang W;Zhao LJ;Tan YX;Ren H;Qi ZT

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microRNA(miRNA)的失调通常与多种癌症相关,包括肝细胞癌(HCC)。在这项研究中,我们鉴定了10种上调的miRNAs,(miR-217、miR-518 b、miR-517 c、miR-520 g、miR-519 a、miR-522、miR-518 e、miR-525- 3 p、miR-512- 3 p和miR-518 a-3 p)和10种下调的miRNA(miR-138、miR-214、miR-214#、miR-27a#、miR-199a_5p、miR-433、miR-511、miR-592、miR-483- 5 p和miR-483- 3 p)通过Taqman miRNAs阵列和定量实时PCR(qRT-PCR)确认。此外,我们研究了miR-138在HCC中的表达和可能的作用。qRT-PCR结果显示77.8%(14/18)的HCC组织中miR-138表达较癌旁组织下调。miR-138过表达通过诱导HCC细胞系中的细胞停滞降低细胞活力和集落形成,并抑制异种移植裸鼠中的肿瘤细胞生长。miR-138抑制剂的使用增加了HCC细胞系中的细胞活力和集落形成以及异种移植裸鼠中的肿瘤细胞生长。使用TargetScan预测,CCND 3被定义为miR-138的潜在直接靶标。此外,在HCC组织中观察到CCND 3蛋白表达与miR-138表达呈负相关。双荧光素酶报告基因检测结果表明,CCND 3是miR-138的直接靶点。使用miR-138模拟物或抑制剂可以降低或增加HCC细胞系中的CCND 3蛋白水平。我们的结论是,频繁下调的miR-138可以调节CCND 3,并在HCC中作为肿瘤抑制因子发挥作用。因此,miR-138可能作为一种有用的治疗剂用于基于miRNA的HCC治疗。
The deregulation of microRNA (miRNA) is frequently associated with a variety of cancers, including hepatocellular carcinoma (HCC). In this study, we identified 10 upregulated miRNAs (miR-217, miR-518b, miR-517c, miR-520g, miR-519a, miR-522, miR-518e, miR-525-3p, miR-512-3p and miR-518a-3p) and 10 downregulated miRNAs (miR-138, miR-214, miR-214#, miR-27a#, miR-199a-5p, miR-433, miR-511, miR-592, miR-483-5p and miR-483-3p) by Taqman miRNAs array and quantitative real-time PCR (qRT–PCR) confirmation. Additionally, we investigated the expression and possible role of miR-138 in HCC. qRT–PCR results showed that miR-138 was downregulated in 77.8%(14/18) of HCC tissues compared with adjacent non-tumor tissues. Overexpression of miR-138 reduced cell viability and colony formation by induction of cell arrest in HCC cell lines and inhibited tumor cell growth in xenograft nude mice. The use of miR-138 inhibitor increased cell viability and colony formation in HCC cell lines and tumor cell growth in xenograft nude mice. Using TargetScan predictions, CCND3 was defined as a potential direct target of miR-138. Furthermore, CCND3 protein expression was observed to be negatively correlated with miR-138 expression in HCC tissues. The dual-luciferase reporter gene assay results showed that CCND3 was a direct target of miR-138. The use of miR-138 mimic or inhibitor could decrease or increase CCND3 protein levels in HCC cell lines. We conclude that the frequently downregulated miR-138 can regulate CCND3 and function as a tumor suppressor in HCC. Therefore, miR-138 may serve as a useful therapeutic agent for miRNA-based HCC therapy.
miR-16 家族通过调节多个细胞周期基因诱导细胞周期停滞。
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发表时间: 2008-09
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发表时间: 2007-10-01
期刊: GENOME RESEARCH
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MicroRNA-138 抑制鳞状细胞癌细胞系的上皮间质转化。
DOI: 10.1042/bj20111006
发表时间: 2011-11-15
期刊: The Biochemical journal
影响因子: --
作者:
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DOI: 10.1158/0008-5472.can-10-3951
发表时间: 2011-05-15
期刊: Cancer research
影响因子: 11.2
作者:
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