School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong.
J Cell Biochem. 2014 Apr;115(4):744-53. doi: 10.1002/jcb.24714.
FHL2 is a LIM domain protein that is able to form various protein complexes and regulate gene transcription. Recent findings showed that FHL2 is a potential tumor suppressor gene that was down-regulated in hepatocellular carcinoma. In the present study, microarray profiling of gene expression was performed to identify the genes regulated by FHL2 in mouse livers. The differentially expressed genes were further analyzed by bioinformatics tools including DAVID, KEGG, and STRING. Our data illustrate that FHL2 affects genes involved in various functions including signal transduction, responses to external stimulus, cancer-related pathways, cardiovascular function and regulation of actin cytoskeleton. Moreover, a network of differentially expressed genes identified in this study and known FHL2-interacting proteins was constructed. Then, genes identified by bioinformatics tools and most functional relevant to FHL2 were selected for further validation. Finally, the differential expression of Ar, Id3, Inhbe, Alas1, Bcl6, Pparδ, Angptl4, and Erbb4 were confirmed by quantitative real-time PCR. In summary, we have established a database of genes that are potentially regulated by FHL2 and these genes should be future targets for the elucidation of functional roles of FHL2.
FHL2 是一个 LIM 结构域蛋白，能够形成各种蛋白质复合物并调节基因转录。最近的研究发现，FHL2 是一种潜在的肿瘤抑制基因，在肝癌中下调。在本研究中，通过基因表达微阵列分析鉴定 FHL2 在小鼠肝脏中调节的基因。通过 DAVID、KEGG 和 STRING 等生物信息学工具进一步分析差异表达基因。我们的数据表明，FHL2 影响涉及各种功能的基因，包括信号转导、对外界刺激的反应、癌症相关途径、心血管功能和肌动蛋白细胞骨架的调节。此外，构建了一个包含本研究中鉴定的差异表达基因和已知与 FHL2 相互作用的蛋白质的网络。然后，选择通过生物信息学工具鉴定的与 FHL2 最相关的基因进行进一步验证。最后，通过定量实时 PCR 验证了 Ar、Id3、Inhbe、Alas1、Bcl6、Pparδ、Angptl4 和 Erbb4 的差异表达。总之，我们建立了一个可能由 FHL2 调节的基因数据库，这些基因应该是阐明 FHL2 功能作用的未来目标。
