Bai Yunfei, Xue Ying, Xie Xueying, Yu Tong, Zhu Yihua, Ge Qinyu, Lu Zuhong
School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, China.
School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, China.
Gene. 2014 Sep 10;548(1):91-100. doi: 10.1016/j.gene.2014.07.016. Epub 2014 Jul 9.
Understanding miRNAs' regulatory networks and target genes could facilitate the development of therapies for human diseases such as cancer. Although much useful gene expression profiling data for tumor cell lines is available, microarray data for miRNAs and mRNAs in the human HepG2 cell line have only been compared with that of other cell lines separately. The relationship between miRNAs and mRNAs in integrated expression profiles for HepG2 cells is still unknown. To explore the miRNA-mRNA correlations in hepatocellular carcinoma (HCC) cells, we performed miRNA and mRNA expression profiling in HepG2 cells and normal liver HL-7702 cells at the genome scale using next-generation sequencing technology. We identified 193 miRNAs that are differentially expressed in these two cell lines. Of these, 89 miRNAs were down-regulated in HepG2 cells compared with HL-7702 cells, while 104 miRNAs were up-regulated. We also observed 3035 mRNAs that are significantly dys-regulated in HepG2 cells. We then performed an integrated analysis of the expression data for differentially expressed miRNAs and mRNAs and found several miRNA-mRNA pairs that are significantly correlated in HepG2 cells. Further analysis suggested that these differentially expressed genes were enriched in four tumorigenesis-related signaling pathways, namely, ErbB, JAK-STAT, mTOR, and WNT, which until now had not been fully reported. Our results could be helpful in understanding the mechanisms of HCC occurrence and development.
了解微小RNA（miRNA）的调控网络和靶基因有助于开发针对癌症等人类疾病的治疗方法。尽管有大量关于肿瘤细胞系的有用基因表达谱数据，但人类肝癌细胞系HepG2中miRNA和mRNA的微阵列数据仅分别与其他细胞系的数据进行了比较。HepG2细胞综合表达谱中miRNA与mRNA之间的关系仍然未知。为了探究肝细胞癌（HCC）细胞中miRNA与mRNA的相关性，我们使用下一代测序技术在基因组规模上对HepG2细胞和正常肝HL-7702细胞进行了miRNA和mRNA表达谱分析。我们鉴定出193个在这两种细胞系中差异表达的miRNA。其中，与HL-7702细胞相比，89个miRNA在HepG2细胞中表达下调，而104个miRNA表达上调。我们还观察到3035个在HepG2细胞中显著失调的mRNA。然后，我们对差异表达的miRNA和mRNA的表达数据进行了综合分析，发现了几个在HepG2细胞中显著相关的miRNA-mRNA对。进一步分析表明，这些差异表达的基因富集在四个与肿瘤发生相关的信号通路中，即表皮生长因子受体（ErbB）、Janus激酶-信号转导子和转录激活子（JAK-STAT）、哺乳动物雷帕霉素靶蛋白（mTOR）和Wnt信号通路，而这些通路此前尚未得到充分报道。我们的结果可能有助于理解HCC发生和发展的机制。
