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A novel function of HRP-3 in regulating cell cycle progression via the HDAC-E2F1-Cyclin E pathway in lung cancer.
- Source :
-
Cancer science [Cancer Sci] 2022 Jan; Vol. 113 (1), pp. 145-155. Date of Electronic Publication: 2021 Nov 10. - Publication Year :
- 2022
-
Abstract
- To improve the poor survival rate of lung cancer patients, we investigated the role of HDGF-related protein 3 (HRP-3) as a potential biomarker for lung cancer. The expression of endogenous HRP-3 in human lung cancer tissues and xenograft tumor models is indicative of its clinical relevance in lung cancer. Additionally, we demonstrated that HRP-3 directly binds to the E2F1 promoter on chromatin. Interestingly, HRP-3 depletion in A549 cells impedes the binding of HRP-3 to the E2F1 promoter; this in turn hampers the interaction between Histone H3/H4 and HDAC1/2 on the E2F1 promoter, while concomitantly inducing Histone H3/H4 acetylation around the E2F1 promoter. The enhanced Histone H3/H4 acetylation on the E2F1 promoter through HRP-3 depletion increases the transcription level of E2F1. Furthermore, the increased E2F1 transcription levels lead to the enhanced transcription of Cyclin E, known as the E2F1-responsive gene, thus inducing S-phase accumulation. Therefore, our study provides evidence for the utility of HRP-3 as a biomarker for the prognosis and treatment of lung cancer. Furthermore, we delineated the capacity of HRP-3 to regulate the E2F1 transcription level via histone deacetylation.<br /> (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
- Subjects :
- A549 Cells
Animals
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms genetics
Lung Neoplasms metabolism
Mice
Neoplasm Transplantation
Promoter Regions, Genetic
Signal Transduction
Biomarkers, Tumor metabolism
Cyclin E metabolism
E2F1 Transcription Factor genetics
Histone Deacetylases metabolism
Intracellular Signaling Peptides and Proteins metabolism
Lung Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1349-7006
- Volume :
- 113
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cancer science
- Publication Type :
- Academic Journal
- Accession number :
- 34714604
- Full Text :
- https://doi.org/10.1111/cas.15183