Changes in microRNAs associated with Twist-1 and Bcl-2 overexpression identify signaling pathways.
Epithelial-mesenchymal transition (EMT) is regulated by multiple signal transduction pathways. Twist-1 is one of the most important transcription factors in these pathways. In a previous study, we found that Bcl-2 enhanced the role of Twist-1 in EMT. Coexpression of Twist-1 and Bcl-2 may play an import role in vasculogenic mimicry (VM) through regulation of EMT. Moreover, regulators of EMT and VM are known to be important targets for microRNAs (miRNAs). To better understand how these critical pathways are induced by coexpression of Twist-1 and Bcl-2, we performed a comprehensive comparative bioinformatics analysis using microarrays on HCCs that overexpressed Twist-1 and Bcl-2. Eleven miRNAs associated with coexpression of Twist-1 and Bcl-2 were selected from the comprehensive analysis of miRNA microarray and ChIP-seq analysis. Changes in miRNAs were associated with significant differences in the expression of genes involved in signal transduction pathways related to processes including tumor invasion, metastasis, angiogenesis, and tumor cell shape. We confirmed the role of Twist-1 and Bcl-2 coexpression in HCC cells using wound healing assays, invasion assays, and 3D Matrigel assays. Furthermore, the role of miR-27a as a crucial regulator of EMT and VM was confirmed in HCC cells by RT-PCR and western blot analysis. These findings provide evidence that Bcl-2 enhances the role of Twist-1 in VM and EMT through miRNAs.
Department of Pathology, Tianjin Medical University, Tianjin 300070, China; Department of Pathology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
Nan
N
Zhao
Department of Pathology, Tianjin Medical University, Tianjin 300070, China; Department of Pathology, General Hospital of Tianjin Medical University, Tianjin 300052, China; Department of Pathology, Cancer Hospital of Tianjin Medical University, Tianjin 300060, China. Electronic address: sunbaocun@aliyun.com.
Bao-cun
BC
Sun
Department of Pathology, Tianjin Medical University, Tianjin 300070, China; Department of Pathology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
Xiu-lan
XL
Zhao
Department of Pathology, Tianjin Medical University, Tianjin 300070, China.
Yong
Y
Wang
Department of Pathology, Tianjin Medical University, Tianjin 300070, China.
Hui-zhi
HZ
Sun
Department of Pathology, Tianjin Medical University, Tianjin 300070, China; Department of Pathology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
Xue-yi
XY
Dong
Department of Pathology, Tianjin Medical University, Tianjin 300070, China; Department of Pathology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
Jie
J
Meng
Department of Pathology, Tianjin Medical University, Tianjin 300070, China; Department of Pathology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
Qiang
Q
Gu
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics*
C000595707:BCL2 protein, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1
Bcl-2; EMT; Twist-1; VM; miRNAs