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慢性乙型肝炎与肝细胞癌之间的微泡微小RNA谱及其功能作用

Microvesicle microRNA profiles and functional roles between chronic hepatitis B and hepatocellular carcinoma.

作者信息

Li H, Sun L, Chen X, Xiong W, Hu D, Jie S

机构信息

Center for Stem Cell Research and Application, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.

出版信息

Clin Transl Oncol. 2014 Mar;16(3):315-21. doi: 10.1007/s12094-013-1078-1. Epub 2013 Jul 18.

Abstract

OBJECTIVES

Hepatocellular carcinoma (HCC) is an inflammation-related malignancy and chronic hepatitis B (CHB) predisposes to HCC. Microvesicles (MVs) transfer various bioactive molecules including microRNA (miRNA) between cells and exert biological functions. The purpose of this study was to detect CHB-MV and HCC-MV miRNAs and analyze the expression profiles and functional roles between CHB and HCC.

METHODS

We examined MV miRNA profiles of CHB and HCC using miRNA microarrays. TargetScan, PicTar and miRanda were exerted to predict target genes regulating these differentially expressed miRNAs.

RESULTS

A total of 272 and 242 aberrant fluctuation miRNAs were identified in CHB-MVs and HCC-MVs, respectively. Among them, there were 53 miRNAs co-expressing both in CHB-MVs and HCC-MVs. These miRNAs affected cellular apoptosis, proliferation and molecular signaling pathways. Among them, 25 co-expressed MV miRNAs targeted 21 inflammatory factors and these miRNAs may be a tight linkage between CHB and HCC. Interestingly, there were 14 co-expressed MV miRNAs targeting 17 oncogenes and 7 miRNAs targeting 9 tumor suppressors in the study. In addition, MVs were enriched with maladjusted miRNAs regulating zinc finger proteins and chromosome open reading frame. Those MV miRNAs may play roles in CHB developing to HCC.

CONCLUSIONS

We demonstrated that CHB and HCC displayed aberrantly co-expressed MV miRNA profiles for the first time, which may have a link between CHB and HCC. Those MV miRNAs may serve as early biomarkers for HCC and may aid to promote CHB developing to HCC.

摘要

目的

肝细胞癌(HCC)是一种与炎症相关的恶性肿瘤,慢性乙型肝炎(CHB)易引发HCC。微泡(MVs)在细胞间传递包括微小RNA(miRNA)在内的各种生物活性分子并发挥生物学功能。本研究旨在检测CHB-MV和HCC-MV的miRNAs,并分析CHB与HCC之间的表达谱及功能作用。

方法

我们使用miRNA微阵列检测CHB和HCC的MV miRNA谱。运用TargetScan、PicTar和miRanda预测调控这些差异表达miRNAs的靶基因。

结果

在CHB-MVs和HCC-MVs中分别鉴定出272个和242个异常波动的miRNAs。其中,有53个miRNAs在CHB-MVs和HCC-MVs中共同表达。这些miRNAs影响细胞凋亡、增殖及分子信号通路。其中,25个共同表达的MV miRNAs靶向21种炎症因子,这些miRNAs可能是CHB与HCC之间的紧密联系。有趣的是,本研究中有14个共同表达的MV miRNAs靶向17个癌基因,7个miRNAs靶向9个肿瘤抑制基因。此外,MVs富含调控锌指蛋白和染色体开放阅读框的失调miRNAs。这些MV miRNAs可能在CHB发展为HCC过程中发挥作用。

结论

我们首次证明CHB和HCC显示出异常共同表达的MV miRNA谱,这可能是CHB与HCC之间的一种联系。这些MV miRNAs可能作为HCC的早期生物标志物,并可能有助于促进CHB发展为HCC。

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