| RRC ID |
78235
|
| 著者 |
Imanishi M, Inoue T, Fukushima K, Yamashita R, Nakayama R, Nojima M, Kondo K, Gomi Y, Tsunematsu H, Goto K, Miyamoto L, Funamoto M, Denda M, Ishizawa K, Otaka A, Fujino H, Ikeda Y, Tsuchiya K.
|
| タイトル |
CA9 and PRELID2; hypoxia-responsive potential therapeutic targets for pancreatic ductal adenocarcinoma as per bioinformatics analyses.
|
| ジャーナル |
J Pharmacol Sci
|
| Abstract |
A strong hypoxic environment has been observed in pancreatic ductal adenocarcinoma (PDAC) cells, which contributes to drug resistance, tumor progression, and metastasis. Therefore, we performed bioinformatics analyses to investigate potential targets for the treatment of PDAC. To identify potential genes as effective PDAC treatment targets, we selected all genes whose expression level was related to worse overall survival (OS) in The Cancer Genome Atlas (TCGA) database and selected only the genes that matched with the genes upregulated due to hypoxia in pancreatic cancer cells in the dataset obtained from the Gene Expression Omnibus (GEO) database. Although the extracted 107 hypoxia-responsive genes included the genes that were slightly enriched in angiogenic factors, TCGA data analysis revealed that the expression level of endothelial cell (EC) markers did not affect OS. Finally, we selected CA9 and PRELID2 as potential targets for PDAC treatment and elucidated that a CA9 inhibitor, U-104, suppressed pancreatic cancer cell growth more effectively than 5-fluorouracil (5-FU) and PRELID2 siRNA treatment suppressed the cell growth stronger than CA9 siRNA treatment. Thus, we elucidated that specific inhibition of PRELID2 as well as CA9, extracted via exhaustive bioinformatic analyses of clinical datasets, could be a more effective strategy for PDAC treatment.
|
| 巻・号 |
153(4)
|
| ページ |
232-242
|
| 公開日 |
2023-12-1
|
| DOI |
10.1016/j.jphs.2023.10.003
|
| PII |
S1347-8613(23)00063-4
|
| PMID |
37973221
|
| MeSH |
Antigens, Neoplasm / genetics
Antigens, Neoplasm / metabolism
Antigens, Neoplasm / therapeutic use
Carbonic Anhydrase IX / genetics
Carbonic Anhydrase IX / metabolism
Carcinoma, Pancreatic Ductal* / drug therapy
Carcinoma, Pancreatic Ductal* / genetics
Computational Biology
Humans
Hypoxia / metabolism
Pancreatic Neoplasms* / drug therapy
Pancreatic Neoplasms* / genetics
RNA, Small Interfering
|
| リソース情報 |
| ヒト・動物細胞 |
PANC-1(RCB2095) |
