Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Gene. 2018 Nov 30;677:340-348. doi: 10.1016/j.gene.2018.08.013. Epub 2018 Aug 11.
SKT11, an important tumor suppressor, is a member of the serine/threonine kinase family and plays a crucial role in tumor invasion and metastasis by activated adenine monophosphate-activated protein kinase (AMPK) and AMPK-related kinase proteins. However, few studies have elaborated its regulations of development and metabolism of cartilage, as well as skeleton. This study was aimed to investigate the role of Stk11-knockout in chondrocyte by bioinformatics analysis. The gene expression profiles for Stk11-knockout and wild-type mice were downloaded from the Gene Expression Omnibus (GEO) database. A total of 1104 differentially expressed genes (DEGs) were identified by Affymetrix Expression Console and Transcriptome Analysis Console (TAC) software, including 560 up-regulated and 544 down-regulated genes. The protein-protein interaction (PPI) networks were built by mapping DEGs into STRING, in which hub genes such as Fos, Pdgfrb, Pdgfra, Flt1/Vegfr1, Smad3, Mapk14, Twist and Aurkb were further identified. For the up-regulated genes, PI3K-AKT signaling pathway and Wnt signaling pathway were two main pathways in the KEGG analysis, and ossification and extracellular matrix organization were involved in the Gene Ontology (GO) analysis. On the other hand, the down-regulated genes were mainly involved in systemic lupus erythematosus and alcoholism pathways, and B cell receptor signaling pathway and immune system process biological processes. MiRNA-9, miRNA-134, miRNA-492, miRNA-224 and miRNA-142-5p were identified as key regulators in the miRNAs-DEG regulatory network. Additionally, OSF2/RUNX2, and NFAT regulated DEGs collectively in the transcription factor regulatory network. The results of RT-PCR verified that the expression of hub genes, transcription factors and miRNAs in our experiment were basically consistent with the microarray hybridization. In this study, we provide an insight into the role of Stk11 in chondrocyte and identify novel genes related to Stk11.
SKT11 是丝氨酸/苏氨酸激酶家族的重要肿瘤抑制因子，通过激活腺嘌呤单磷酸激活蛋白激酶 (AMPK) 和 AMPK 相关激酶蛋白在肿瘤侵袭和转移中发挥关键作用。然而，很少有研究详细阐述了其对软骨和骨骼发育和代谢的调节作用。本研究旨在通过生物信息学分析研究 Stk11 敲除在软骨细胞中的作用。从基因表达综合数据库 (GEO) 数据库下载 Stk11 敲除和野生型小鼠的基因表达谱。使用 Affymetrix Expression Console 和 Transcriptome Analysis Console (TAC) 软件鉴定出 1104 个差异表达基因 (DEGs)，包括 560 个上调基因和 544 个下调基因。通过将 DEGs 映射到 STRING 构建蛋白质-蛋白质相互作用 (PPI) 网络，进一步鉴定出 Fos、Pdgfrb、Pdgfra、Flt1/Vegfr1、Smad3、Mapk14、Twist 和 Aurkb 等关键基因。对于上调基因，KEGG 分析中主要涉及 PI3K-AKT 信号通路和 Wnt 信号通路，GO 分析中涉及骨化和细胞外基质组织。另一方面，下调基因主要涉及系统性红斑狼疮和酒精中毒途径，以及 B 细胞受体信号通路和免疫系统过程的生物学过程。miRNA-9、miRNA-134、miRNA-492、miRNA-224 和 miRNA-142-5p 被鉴定为 miRNA-DEG 调控网络中的关键调节因子。此外，OSF2/RUNX2 和 NFAT 共同调节转录因子调控网络中的 DEGs。RT-PCR 验证结果表明，我们实验中关键基因、转录因子和 miRNA 的表达与微阵列杂交基本一致。本研究深入探讨了 Stk11 在软骨细胞中的作用，并鉴定出与 Stk11 相关的新基因。
