Shuyi Zhou1, Yuanliang Yan1, Xi Chen1, Xiang Wang1, Shuangshuang Zeng1, Long Qian1, Jie Wei1, Xue Yang1, Yangying Zhou2, Zhicheng Gong3, Zhijie Xu4. 1. Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China. 2. Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China. 3. Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China. Electronic address: gongzhicheng@csu.edu.cn. 4. Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China. Electronic address: xzj1322007@csu.edu.cn.
Abstract
BACKGROUND: Phosphoribosylaminoimidazole carboxylase (PAICS), a de novo purine metabolic enzyme, has been identified as an oncogene in several tumor types, including breast cancer and prostate cancer. However, the role of PAICS in human lung adenocarcinoma (LADC) requires further study. METHODS: In this research, the effects of PAICS on the occurrence and prognosis of LADC were evaluated using integrative bioinformatics analyses. RESULTS: By employing the bioinformatics analyses of several public databases, PAICS, which is overexpressed in the LADC tissues, was identified as a potential tumor-promoting gene in LADC biology. Several relevant clinical studies indicated that the upregulation of PAICS was statistically correlated with a shorter overall survival time. Moreover, the carcinogenic function of PAICS in LADC was validated by the further protein-protein interactions (PPI) and biological process annotation analysis. Mechanistically, we found that the PAICS methylation level was significantly lower in the LADC tissues compared to the normal lung tissues. Furthermore, using the MEXPRESS web tool, we predicted 15 possible DNA methylation sites in the nucleotide sequences of PAICS, which could explain the alteration in the PAICS expression levels in LADC. CONCLUSIONS: Our work demonstrates that high levels of PAICS are found in LADC and that this gene may be a potential therapeutic target for this subset of lung cancers. Determining the detailed roles of PAICS in LADC biology may provide useful information for further investigations.
BACKGROUND:Phosphoribosylaminoimidazole carboxylase (PAICS), a de novo purine metabolic enzyme, has been identified as an oncogene in several tumor types, including breast cancer and prostate cancer. However, the role of PAICS in humanlung adenocarcinoma (LADC) requires further study. METHODS: In this research, the effects of PAICS on the occurrence and prognosis of LADC were evaluated using integrative bioinformatics analyses. RESULTS: By employing the bioinformatics analyses of several public databases, PAICS, which is overexpressed in the LADC tissues, was identified as a potential tumor-promoting gene in LADC biology. Several relevant clinical studies indicated that the upregulation of PAICS was statistically correlated with a shorter overall survival time. Moreover, the carcinogenic function of PAICS in LADC was validated by the further protein-protein interactions (PPI) and biological process annotation analysis. Mechanistically, we found that the PAICS methylation level was significantly lower in the LADC tissues compared to the normal lung tissues. Furthermore, using the MEXPRESS web tool, we predicted 15 possible DNA methylation sites in the nucleotide sequences of PAICS, which could explain the alteration in the PAICS expression levels in LADC. CONCLUSIONS: Our work demonstrates that high levels of PAICS are found in LADC and that this gene may be a potential therapeutic target for this subset of lung cancers. Determining the detailed roles of PAICS in LADC biology may provide useful information for further investigations.
Authors: Huanzhou Xu; Ramon D Perez; Tiffany R Frey; Eric M Burton; Sudha Mannemuddhu; John D Haley; Michael T McIntosh; Sumita Bhaduri-McIntosh Journal: PLoS Pathog Date: 2019-12-16 Impact factor: 6.823