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Elucidating the role of EPPK1 in lung adenocarcinoma development

Authors :
Ken Arimura
Michael Kammer
S. M. Jamshedur Rahman
Chen Sheau-Chiann
Shilin Zhao
Chen Heidi
Rosana Eisenberg
Yong Zou
Sanja Antic
Bradley Richmond
Etsuko Tagaya
Eric Grogan
Pierre Massion
Fabien Maldonado
Source :
BMC Cancer, Vol 24, Iss 1, Pp 1-13 (2024)
Publication Year :
2024
Publisher :
BMC, 2024.

Abstract

Abstract 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.

Details

Language :
English
ISSN :
14712407
Volume :
24
Issue :
1
Database :
Directory of Open Access Journals
Journal :
BMC Cancer
Publication Type :
Academic Journal
Accession number :
edsdoj.887a0fd0014d37a1ebaaccf119ec41
Document Type :
article
Full Text :
https://doi.org/10.1186/s12885-024-12185-x