Integrated analysis of transcriptome data revealed MMP3 and MMP13 as critical genes in anaplastic thyroid cancer progression.

Abstract

To better understand the molecular mechanisms of anaplastic thyroid carcinoma (ATC), we aimed to identify the hub genes specifically involved in ATC by integrated bioinformatics analysis. In this study, using three Gene Expression Omnibus data sets with the same platform GPL570, we screened hub genes involved in ATC progression. In vitro experiments, such as western blot analysis, Transwell assays, and coimmunoprecipitation, was performed to verify our findings. By comparing three subtypes of thyroid cancer with normal tissue, we found ATC harbored more changed genes than well and poorly differentiated thyroid cancer. Using specifically differentially expressed genes between ATC and normal thyroid tissues to perform Gene ontology (GO) analysis, ATC showed enrichments of GO terms involved in lymphocyte migration and activation, collagen catabolic and metabolic process, thyroid hormone synthesis, and embolism. Using genes involved in extracellular matrix, coexpression network analysis and protein-protein interaction analysis were performed to identify matrix metalloproteinase 3 (MMP3) and MMP13 as two hub genes. Our experimental data indicated that both MMP3 and MMP13 were upregulated in ATC and knockdown of either of them could notably suppress ATC cell invasion and migration. Mechanistically, Gene Set Enrichment Analysis, coimmunoprecipitation, and rescue experiments revealed MMP3 and MMP13 not only interacted with each other, but also regulated each other through the janus kinase/signal transducer and activator of transcription 3 and mammalian target of rapamycin pathways. In conclusion, we identified a specific molecular mechanisms for the development of ATC by integrated analysis of transcriptome and in vitro experiments, which suggested that MMP3 and MMP13 might be developed as novel therapeutic targets for ATC.

• Authors: Yuehua Ma, Shundong Cang, Guoqing Li, Yong Su, Huifeng Zhang, Limin Wang, Junpeng Yang, Xiaoyang Shi, Guijun Qin, Huijuan Yuan
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 234 Issue 12 Pg. 22260-22271 (12 2019) ISSN: 1097-4652 [Electronic] United States
• PMID: 31081124 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• STAT3 Transcription Factor
• Janus Kinases
• TOR Serine-Threonine Kinases
• Matrix Metalloproteinase 13
• Matrix Metalloproteinase 3

Topics

• Cell Line, Tumor
• Cell Movement (genetics)
• Disease Progression
• Gene Expression Regulation, Neoplastic
• Gene Ontology
• Humans
• Janus Kinases (metabolism)
• Matrix Metalloproteinase 13 (metabolism)
• Matrix Metalloproteinase 3 (metabolism)
• Models, Biological
• Neoplasm Invasiveness
• Principal Component Analysis
• Protein Binding
• STAT3 Transcription Factor (metabolism)
• Signal Transduction
• TOR Serine-Threonine Kinases (metabolism)
• Thyroid Carcinoma, Anaplastic (genetics, pathology)
• Transcriptome (genetics)
• Up-Regulation (genetics)