miR-10b is overexpressed in hepatocellular carcinoma and promotes cell proliferation, migration and invasion through RhoC, uPAR and MMPs.
miR-10b is overexpressed in hepatocellular carcinoma and promotes cell proliferation, migration and invasion through RhoC, uPAR and MMPs.
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miR-10b在肝细胞癌中过表达并通过RhoC、uPAR和MMP促进细胞增殖、迁移和侵袭
DOI：
10.1186/s12967-014-0234-x
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发表时间：
2014-09-19
影响因子：
7.4
通讯作者：
Lu N
中科院分区：
文献类型：
--
作者：
Liao CG;Kong LM;Zhou P;Yang XL;Huang JG;Zhang HL;Lu N
研究背景miR-10 b是近年来发现的一种在多种人类肿瘤中高表达的miRNA，可促进细胞的迁移和侵袭。然而，miR-10 b在肝细胞癌（HCC）中的具体功能目前尚不清楚。方法检测60例配对的不同TNM分期HCC肿瘤组织中miR-10 b的表达水平，并与癌旁非肿瘤（ANT）组织、正常组织对照进行比较良性肿瘤8例，正常肝组织7例，应用实时荧光定量RT-PCR技术检测3例正常肝组织和7例肝癌细胞系的肝癌细胞分化程度，并分析其与肝癌临床病理特征的关系。采用侵袭实验、MTT增殖实验和创伤愈合实验检测转染后肝癌细胞的侵袭和增殖能力。miR-10 b对肝癌的影响在体内通过小鼠异种移植模型进行验证。结果我们发现miR-10 b在人肝癌组织和细胞系中的表达分别比正常对照组增加。miR-10 b的表达与肝癌转移能力相关。MHCC-97 L细胞中miR-10 b的过表达增加了细胞运动性和侵袭力，而MHCC-97 H细胞中miR-10 b的抑制则降低了体外和体内细胞运动性和侵袭力。我们还通过荧光素酶报告基因检测发现，HOXD 10在转录后水平受到miR-10 b的负调控。结论miR-10 b在HCC中过表达，并通过HOXD 10/ RhoC/uPAR/ MMPs通路促进HCC细胞的迁移和侵袭，可能为HCC的治疗提供新的生物靶点。
BackgroundRecently, miR-10b is identified as a miRNA highly expressed in many human cancers, promoting cell migration and invasion. However, the specific function of miR-10b in hepatocellular carcinoma (HCC) is unclear at this point.MethodsThe miR-10b expression levels in 60 paired different TNM Stage HCC tumor tissues compared with adjacent non-tumor (ANT) tissues, normal tissue control (8 benign tumor and 7 normal liver tissues), 3 normal liver and 7 HCC cell lines were measured by real-time quantitative RT-PCR and to evaluate their association with HCC clinicopathologic features. Invasion assay, MTT proliferation assay and wound-healing assay were performed to test the invasion and proliferation of HCC cell after transfection. The effect of miR-10b on HCCin vivowas validated by murine xenograft model.ResultsWe found that miR-10b expression was increased in human HCC tissues and cell lines compared with normal control, respectively. The expression of miR-10b was correlated with HCC metastatic ability. Overexpression of miR-10b in MHCC-97L cells increased cell motility and invasiveness, whereas inhibition of miR-10b in MHCC-97H cells reduced cell motility and invasivenessin vitroandin vivo. We also showed that HOXD10 was negatively regulated by miR-10b at the posttranscriptional level, via a specific target site within the 3′UTR by luciferase reporter assay. Furthermore, we found that miR-10b induced HCC cell invasion and migration by modulating the HOXD10 target gene RhoC, uPAR, MMP-2 and MMP-9 expression.ConclusionsOur results suggested that miR-10b was overexpressed in HCC and promoted HCC cell migration and invasion through the HOXD10/ RhoC/ uPAR/ MMPs pathway which may provide a novel bio-target for HCC therapy.
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影响因子：
5.7
作者：
Chai, Guolin;Liu, Ning;Yu, Xijie
通讯作者：
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影响因子：
5
作者：
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通讯作者：
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影响因子：
64.8
作者：
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通讯作者：
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64.8
作者：
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通讯作者：
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影响因子：
11.2
作者：
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通讯作者：
Merchan JR