RRC ID 78615
Author Ishii D, Shindo Y, Arai W, Konno T, Kohno T, Honda K, Miyajima M, Watanabe A, Kojima T.
Title The Roles and Regulatory Mechanisms of Tight Junction Protein Cingulin and Transcription Factor Forkhead Box Protein O1 in Human Lung Adenocarcinoma A549 Cells and Normal Lung Epithelial Cells.
Journal Int J Mol Sci
Abstract Tight junction (TJ) protein cingulin (CGN) and transcription factor forkhead box protein O1 (FOXO1) contribute to the development of various cancers. Histone deacetylase (HDAC) inhibitors have a potential therapeutic role for some cancers. HDAC inhibitors affect the expression of both CGN and FOXO1. However, the roles and regulatory mechanisms of CGN and FOXO1 are unknown in non-small cell lung cancer (NSCLC) and normal human lung epithelial (HLE) cells. In the present study, to investigate the effects of CGN and FOXO1 on the malignancy of NSCLC, we used A549 cells as human lung adenocarcinoma and primary human lung epithelial (HLE) cells as normal lung tissues and performed the knockdown of CGN and FOXO1 by siRNAs. Furthermore, to investigate the detailed mechanisms in the antitumor effects of HDAC inhibitors for NSCLC via CGN and FOXO1, A549 cells and HLE cells were treated with the HDAC inhibitors trichostatin A (TSA) and Quisinostat (JNJ-2648158). In A549 cells, the knockdown of CGN increased bicellular TJ protein claudin-2 (CLDN-2) via mitogen-activated protein kinase/adenosine monophosphate-activated protein kinase (MAPK/AMPK) pathways and induced cell migration, while the knockdown of FOXO1 increased claudin-4 (CLDN-4), decreased CGN, and induced cell proliferation. The knockdown of CGN and FOXO1 induced cell metabolism in A549 cells. TSA and Quisinostat increased CGN and tricellular TJ protein angulin-1/lipolysis-stimulated lipoprotein receptor (LSR) in A549. In normal HLE cells, the knockdown of CGN and FOXO1 increased CLDN-4, while HDAC inhibitors increased CGN and CLDN-4. In conclusion, the knockdown of CGN via FOXO1 contributes to the malignancy of NSCLC. Both HDAC inhibitors, TSA and Quisinostat, may have potential for use in therapy for lung adenocarcinoma via changes in the expression of CGN and FOXO1.
Volume 25(3)
Published 2024-1-24
DOI 10.3390/ijms25031411
PII ijms25031411
PMID 38338691
PMC PMC10855320
MeSH A549 Cells Adenocarcinoma of Lung* / metabolism Adenocarcinoma of Lung* / pathology Carcinoma, Non-Small-Cell Lung* / metabolism Carcinoma, Non-Small-Cell Lung* / pathology Epithelial Cells / metabolism Forkhead Box Protein O1* / genetics Forkhead Box Protein O1* / metabolism Histone Deacetylase Inhibitors / metabolism Histone Deacetylase Inhibitors / pharmacology Humans Hydroxamic Acids* Lung / pathology Lung Neoplasms* / metabolism Tight Junction Proteins* / metabolism Transcription Factors / metabolism
Resource
Human and Animal Cells A549