アリムラ　ケン   ARIMURA Ken   有村　健    所属   医学部 医学科（東京女子医科大学病院）    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読なし
表題	Elucidating the role of EPPK1 in lung adenocarcinoma development.
掲載誌名	正式名：BMC cancer 略　 称：BMC Cancer ISSNコード：14712407/14712407
掲載区分	国外
巻・号・頁	24(1),pp.441
著者・共著者	Arimura Ken†, Kammer Michael, Rahman S M Jamshedur, Sheau-Chiann Chen, Zhao Shilin, Heidi Chen, Eisenberg Rosana, Zou Yong, Antic Sanja, Richmond Bradley, Tagaya Etsuko, Grogan Eric, Massion Pierre, Maldonado Fabien
担当区分	筆頭著者
発行年月	2024/04
概要	BACKGROUND:We recently found that epiplakin 1 (EPPK1) alterations were present in 12% of lung adenocarcinoma (LUAD) cases and were associated with a poor prognosis in early-stage LUAD when combined with other molecular alterations. This study aimed to identify a probable crucial role for EPPK1 in cancer development.METHODS:EPPK1 mRNA and protein expression was analyzed with clinical variables. Normal bronchial epithelial cell lines were exposed to cigarette smoke for 16 weeks to determine whether EPPK1 protein expression was altered after exposure. Further, we used CRISPR-Cas9 to knock out (KO) EPPK1 in LUAD cell lines and observed how the cancer cells were altered functionally and genetically.RESULTS:EPPK1 protein expression was associated with smoking and poor prognosis in early-stage LUAD. Moreover, a consequential mesenchymal-to-epithelial transition was observed, subsequently resulting in diminished cell proliferation and invasion after EPPK1 KO. RNA sequencing revealed that EPPK1 KO induced downregulation of 11 oncogenes, 75 anti-apoptosis, and 22 angiogenesis genes while upregulating 8 tumor suppressors and 12 anti-cell growth genes. We also observed the downregulation of MYC and upregulation of p53 expression at both protein and RNA levels following EPPK1 KO. Gene ontology enrichment analysis of molecular functions highlighted the correlation of EPPK1 with the regulation of mesenchymal cell proliferation, mesenchymal differentiation, angiogenesis, and cell growth after EPPK1 KO.CONCLUSIONS:Our data suggest that EPPK1 is linked to smoking, epithelial to mesenchymal transition, and the regulation of cancer progression, indicating its potential as a therapeutic target for LUAD.
DOI	10.1186/s12885-024-12185-x
PMID	38594604