Yujia Liu1, Yiwen Zhang1,2, Zhuo Tan2,3, Jiafeng Wang2,3, Ying Hu1, Jiao Sun4, Meihua Bao5, Ping Huang1,2, Minghua Ge2,3, Young Jun Chai6, Chuanming Zheng2,3. 1. Clinical Pharmacy Center, Department of Pharmacy, Zhejiang Provincial People's Hospital; Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China. 2. Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, Hangzhou, China. 3. Department of Head and Neck & Thyroid Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China. 4. Department of Pharmacy, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China. 5. Academician Workstation, School of Stomatology, Changsha Medical University, Changsha, China. 6. Department of Surgery, Seoul National University College of Medicine, Seoul Metropolitan Government, Seoul National University Boramae Medical Center, Transdisciplinary Department of Medicine & Advanced Technology, Seoul National University Hospital, Seoul, Korea.
Abstract
BACKGROUND: Anaplastic thyroid carcinoma (ATC) is an extremely aggressive solid tumor with no effective treatment at present. Because of the rapid growth and aggressiveness, nearly all patients die within six months after developing ATC. Hence, more research regarding novel therapeutic targets for ATC is urgently needed. METHODS: Single-cell RNA sequencing data and microarray data of ATC were retrieved from the Gene Expression Omnibus (GEO) database. Cell clustering was performed using the Seurat package. Then, differential expression and functional enrichment analyses were performed. Gene set enrichment analysis (GSEA) was further used to investigate the functional enrichment of lysyl oxidase (LOX) and bone morphogenetic protein-1 (BMP1). The expression levels of LOX and BMP1 were measured using quantitative real-time PCR and Western blot. LOX and BMP1 were knocked down using si-RNAs. Cell proliferation was evaluated by the CCK-8 and clone formation assays. Cell migration and invasion were assessed by the wound healing assay and Transwell assay, respectively. RESULTS: LOX was upregulated at the single-cell level, as well as in ATC tissues and cell lines. LOX knockdown significantly inhibited ATC cell proliferation. Furthermore, the migration and invasion of ATC cells were remarkably inhibited after LOX inhibition. In addition, BMP1 regulated LOX expression in 8505C cells, while BMP1 overexpression restored the LOX activity blocked by the LOX inhibitor BAPN. BMP1 could also induce the cell proliferation and metastasis of ATC. CONCLUSIONS: LOX/BMP1 mediates the malignant progression of ATC, highlighting the potential application of LOX/BMP1 in the treatment of ATC. This study provides new insights for efficient therapeutic agents based on the LOX/BMP1 axis. 2022 Gland Surgery. All rights reserved.
BACKGROUND: Anaplastic thyroid carcinoma (ATC) is an extremely aggressive solid tumor with no effective treatment at present. Because of the rapid growth and aggressiveness, nearly all patients die within six months after developing ATC. Hence, more research regarding novel therapeutic targets for ATC is urgently needed. METHODS: Single-cell RNA sequencing data and microarray data of ATC were retrieved from the Gene Expression Omnibus (GEO) database. Cell clustering was performed using the Seurat package. Then, differential expression and functional enrichment analyses were performed. Gene set enrichment analysis (GSEA) was further used to investigate the functional enrichment of lysyl oxidase (LOX) and bone morphogenetic protein-1 (BMP1). The expression levels of LOX and BMP1 were measured using quantitative real-time PCR and Western blot. LOX and BMP1 were knocked down using si-RNAs. Cell proliferation was evaluated by the CCK-8 and clone formation assays. Cell migration and invasion were assessed by the wound healing assay and Transwell assay, respectively. RESULTS: LOX was upregulated at the single-cell level, as well as in ATC tissues and cell lines. LOX knockdown significantly inhibited ATC cell proliferation. Furthermore, the migration and invasion of ATC cells were remarkably inhibited after LOX inhibition. In addition, BMP1 regulated LOX expression in 8505C cells, while BMP1 overexpression restored the LOX activity blocked by the LOX inhibitor BAPN. BMP1 could also induce the cell proliferation and metastasis of ATC. CONCLUSIONS: LOX/BMP1 mediates the malignant progression of ATC, highlighting the potential application of LOX/BMP1 in the treatment of ATC. This study provides new insights for efficient therapeutic agents based on the LOX/BMP1 axis. 2022 Gland Surgery. All rights reserved.
Authors: Matthew E Ritchie; Belinda Phipson; Di Wu; Yifang Hu; Charity W Law; Wei Shi; Gordon K Smyth Journal: Nucleic Acids Res Date: 2015-01-20 Impact factor: 16.971
Authors: Ruli Gao; Shanshan Bai; Ying C Henderson; Yiyun Lin; Aislyn Schalck; Yun Yan; Tapsi Kumar; Min Hu; Emi Sei; Alexander Davis; Fang Wang; Simona F Shaitelman; Jennifer Rui Wang; Ken Chen; Stacy Moulder; Stephen Y Lai; Nicholas E Navin Journal: Nat Biotechnol Date: 2021-01-18 Impact factor: 54.908