PMID- 31081124 OWN - NLM STAT- MEDLINE DCOM- 20200615 LR - 20240403 IS - 1097-4652 (Electronic) IS - 0021-9541 (Linking) VI - 234 IP - 12 DP - 2019 Dec TI - Integrated analysis of transcriptome data revealed MMP3 and MMP13 as critical genes in anaplastic thyroid cancer progression. PG - 22260-22271 LID - 10.1002/jcp.28793 [doi] AB - 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. CI - (c) 2019 Wiley Periodicals, Inc. FAU - Ma, Yuehua AU - Ma Y AD - Department of Endocrinology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China. FAU - Cang, Shundong AU - Cang S AD - Department of Oncology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China. FAU - Li, Guoqing AU - Li G AD - Department of Breast Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China. FAU - Su, Yong AU - Su Y AD - Department of Endocrinology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China. FAU - Zhang, Huifeng AU - Zhang H AD - Department of Endocrinology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China. FAU - Wang, Limin AU - Wang L AD - Department of Endocrinology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China. FAU - Yang, Junpeng AU - Yang J AD - Department of Endocrinology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China. FAU - Shi, Xiaoyang AU - Shi X AD - Department of Endocrinology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China. FAU - Qin, Guijun AU - Qin G AD - Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. FAU - Yuan, Huijuan AU - Yuan H AUID- ORCID: 0000-0001-8151-0595 AD - Department of Endocrinology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190512 PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (STAT3 Transcription Factor) RN - EC 2.7.10.2 (Janus Kinases) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.4.24.- (Matrix Metalloproteinase 13) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM EIN - J Cell Physiol. 2024 Apr 3;:. PMID: 38567739 MH - Cell Line, Tumor MH - Cell Movement/genetics MH - *Disease Progression MH - *Gene Expression Regulation, Neoplastic MH - Gene Ontology MH - Humans MH - Janus Kinases/metabolism MH - Matrix Metalloproteinase 13/*metabolism MH - Matrix Metalloproteinase 3/*metabolism MH - Models, Biological MH - Neoplasm Invasiveness MH - Principal Component Analysis MH - Protein Binding MH - STAT3 Transcription Factor/metabolism MH - Signal Transduction MH - TOR Serine-Threonine Kinases/metabolism MH - Thyroid Carcinoma, Anaplastic/*genetics/*pathology MH - Transcriptome/*genetics MH - Up-Regulation/genetics OTO - NOTNLM OT - Integrated bioinformatics analysis OT - MMP13 OT - MMP3 OT - anaplastic thyroid cancer EDAT- 2019/05/14 06:00 MHDA- 2020/06/17 06:00 CRDT- 2019/05/14 06:00 PHST- 2019/01/23 00:00 [received] PHST- 2019/03/30 00:00 [revised] PHST- 2019/04/24 00:00 [accepted] PHST- 2019/05/14 06:00 [pubmed] PHST- 2020/06/17 06:00 [medline] PHST- 2019/05/14 06:00 [entrez] AID - 10.1002/jcp.28793 [doi] PST - ppublish SO - J Cell Physiol. 2019 Dec;234(12):22260-22271. doi: 10.1002/jcp.28793. Epub 2019 May 12.