@article{b81ff72032d54fcfadfffae8d285433a,
title = "In silico repurposing the Rac1 inhibitor NSC23766 for treating PTTG1-high expressing clear cell renal carcinoma",
abstract = "The pituitary tumor-transforming gene 1 (PTTG1), also known as Securin, is considered an oncogene. This study aimed to investigate the role of PTTG1 in clear cell renal cell carcinoma (ccRCC) using in silico bioinformatics approaches. A pan-cancer analysis using The Cancer Genome Atlas (TCGA) data indicated that among all cancer types copy number amplification of PTTG1 gene was most frequently found in ccRCC. However, amplification of PTTG1 gene copy number did not correlate with the increase of mRNA level in ccRCC, and did not predict the patients{\textquoteright} overall survival. Instead, ccRCC was correlated with overexpression of PTTG1 mRNA, and its expression level was stage-dependent increased in cancer patients. An outlier analysis using the Oncomine database suggested that PTTG1 mRNA expression served as a good biomarker for ccRCC. Pathway analysis for upregulated genes enriched in PTTG1-high expressing ccRCC patients found that PTTG1 overexpression was associated with mitotic defects. Mining drug sensitivity data using the Cancer Therapeutics Response Portal (CTRP) discovered that PTTG1-high expressing ccRCC cell lines were susceptible to a Rac1 (Ras-related C3 botulinum toxin substrate 1) inhibitor NSC23766. Therefore, this study provides an in silico insight into the role of PTTG1 in ccRCC, and repurposes the Rac1 inhibitor NSC23766 for treating PTTG1-high expressing ccRCC.",
keywords = "Bioinformatics, Cell cycle, Clear cell renal carcinoma, Drug repurposing, PTTG1, Rac1 inhibitor",
author = "Hsieh, {Yao Yu} and Liu, {Tsang Pai} and Yang, {Pei Ming}",
note = "Funding Information: We thank the financial supported by the “TMU Research Center of Cancer Translational Medicine” from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan. Funding Information: This work was supported by the Ministry of Education of Taiwan [grant number DP2-107-21121-02-C-03]; the Ministry of Science and Technology of Taiwan [MOST108-2314-B-038-010]; the Mackay Memorial Hospital of Taiwan [grant numbers MMH-107-86, MMH-108-86]; and the Taipei Medical University of Taiwan [grant number TMU106-F-005]. Funding Information: This work was supported by the Ministry of Education of Taiwan [grant number DP2-107-21121-02-C-03 ]; the Ministry of Science and Technology of Taiwan [ MOST108-2314-B-038-010 ]; the Mackay Memorial Hospital of Taiwan [grant numbers MMH-107-86 , MMH-108-86 ]; and the Taipei Medical University of Taiwan [grant number TMU106-F-005 ]. Funding Information: This work was supported by the Ministry of Education of Taiwan [grant number DP2-107-21121-02-C-03]; the Ministry of Science and Technology of Taiwan [MOST108-2314-B-038-010]; the Mackay Memorial Hospital of Taiwan [grant numbers MMH-107-86, MMH-108-86]; and the Taipei Medical University of Taiwan [grant number TMU106-F-005]. We thank the financial supported by the ?TMU Research Center of Cancer Translational Medicine? from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan. Publisher Copyright: {\textcopyright} 2019 Elsevier GmbH",
year = "2019",
month = jan,
day = "1",
doi = "10.1016/j.prp.2019.03.002",
language = "English",
volume = "215",
journal = "Pathology Research and Practice",
issn = "0344-0338",
publisher = "Urban und Fischer Verlag GmbH und Co. KG",
number = "6",
}