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肝癌来源微泡与亲本细胞中微小RNA表达谱的比较及其在肝癌中的作用评估

Comparison of microRNA expression profiles in HCC-derived microvesicles and the parental cells and evaluation of their roles in HCC.

作者信息

Xiong Wei, Sun Li-Ping, Chen Xiao-Mei, Li Hui-Yu, Huang Shi-Ang, Jie Sheng-Hua

机构信息

Center for Stem Cell Research and Application, Institute of Hematology, Huazhong University of Science and Technology, Wuhan, 430022, China.

Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

出版信息

J Huazhong Univ Sci Technolog Med Sci. 2013 Jun;33(3):346-352. doi: 10.1007/s11596-013-1122-y. Epub 2013 Jun 17.

Abstract

To determine whether the microRNAs (miRNAs) contained in cancer-derived microvesicles (MVs) mirror those of the parental tumor cells, we compared the miRNA expression profiles of MVs derived from their parental hepatocellular carcinoma (HCC) cells. The presence and levels of 888 miRNAs from SMMC-7721 cells and MVs were detected by Agilent miRNA microarray analysis. Four selected miRNAs were verified by real time qRT-PCR. Furthermore, the genes of the miRNAs were bioinformatically identified to explore potential roles of the miRNAs in HCC microenvironment. Our results showed that miRNAs expression profiles of MVs derived from HCC were significantly changed. Of all the miRNAs tested, 148 miRNAs were co-expressed in MVs and SMMC-7721 cells, only 121 and 15 miRNAs were detected in MVs and SMMC-7721 cells, respectively. Among the 148 co-expressing miRNAs, 48 miRNAs had the similar expression level and 6 of them were supposed to be oncogenic or suppressive miRNAs. According to the target prediction by Quantile Algorithm method, these miRNAs may regulate 3831 genes which were closely related to cell cycle, apoptosis and oncogenesis, and 78 were known tumor suppressors or oncogenes. Gene ontology (GO) analysis indicated that 3831 genes were mainly associated with nucleic acid binding, cell death, cell adhesion. MVs containing miRNAs, released into the HCC microenvironment, bear the characteristic miRNAs of the original cells and might participate in cancer progression.

摘要

为了确定癌症来源的微泡(MVs)中所含的微小RNA(miRNAs)是否与亲代肿瘤细胞的miRNAs一致,我们比较了源自亲代肝癌(HCC)细胞的MVs的miRNA表达谱。通过安捷伦miRNA微阵列分析检测了SMMC-7721细胞和MVs中888种miRNAs的存在及水平。通过实时定量qRT-PCR对4种选定的miRNAs进行了验证。此外,对这些miRNAs的基因进行了生物信息学鉴定,以探索其在肝癌微环境中的潜在作用。我们的结果表明,源自肝癌的MVs的miRNA表达谱发生了显著变化。在所有检测的miRNAs中,有148种在MVs和SMMC-7721细胞中共同表达,分别只有121种和15种在MVs和SMMC-7721细胞中被检测到。在这148种共同表达的miRNAs中,有48种具有相似的表达水平,其中6种被认为是致癌或抑癌miRNAs。根据分位数算法方法进行的靶标预测,这些miRNAs可能调控3831个与细胞周期、凋亡和肿瘤发生密切相关的基因,其中78个是已知的肿瘤抑制因子或癌基因。基因本体(GO)分析表明,3831个基因主要与核酸结合、细胞死亡、细胞黏附相关。含有miRNAs的MVs释放到肝癌微环境中,携带原始细胞的特征性miRNAs,并可能参与癌症进展。

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