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Published on: July 12, 2022
Identification of Skt11-regulated genes in chondrocytes by integrated bioinformatics analysis
Shuang Liang1, Jia-Ming Zhang1, Zheng-Tao Lv1
1Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Abstract:
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.
Insights
This study reveals the role of serine/threonine kinase 11 (STK11) in chondrocytes using bioinformatics. STK11 knockout impacts cartilage development and metabolism by altering gene expression, signaling pathways, and regulatory networks.
Area of Science:
- Molecular Biology
- Bioinformatics
- Skeletal Biology
Background:
- Serine/threonine kinase 11 (STK11) is a tumor suppressor involved in cell signaling.
- Its role in cartilage development and skeletal metabolism remains largely unexplored.
- Understanding STK11's function in chondrocytes is crucial for skeletal health.
Purpose of the Study:
- To investigate the role of STK11 in chondrocytes using bioinformatics analysis.
- To identify differentially expressed genes (DEGs) and regulatory networks affected by STK11 knockout.
- To explore the impact of STK11 on cartilage development and metabolism.
Main Methods:
- Downloaded gene expression profiles of Stk11-knockout and wild-type mice from the GEO database.
- Identified 1104 DEGs using Affymetrix Expression Console and Transcriptome Analysis Console (TAC).
- Constructed protein-protein interaction (PPI) networks using STRING and analyzed pathways via KEGG and GO.
Main Results:
- Identified 560 up-regulated and 544 down-regulated DEGs in Stk11-knockout chondrocytes.
- Key pathways identified include PI3K-AKT and Wnt signaling (up-regulated) and pathways related to immune responses (down-regulated).
- Identified hub genes (e.g., Fos, Pdgfrb), miRNAs (e.g., miRNA-9), and transcription factors (e.g., RUNX2) involved in STK11 regulation.
Conclusions:
- STK11 plays a significant role in chondrocyte function, impacting skeletal development and metabolism.
- Identified novel genes, signaling pathways, and regulatory networks associated with STK11 in chondrocytes.
- Provides a foundation for further research into STK11's role in skeletal diseases.
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