A novel function of HRP-3 in regulating cell cycle progression via the HDAC-E2F1-Cyclin E pathway in lung cancer.

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.
Authors	Hong Shik Yun, Janet Lee, Ju-Young Kim, Ye-Ji Sim, Chang-Woo Lee, Jong Kuk Park, Jae-Sung Kim, Jiyeon Ahn, Jie-Young Song, Jeong-Hwa Baek, Sang-Gu Hwang
Journal	Cancer science (Cancer Sci) Vol. 113 Issue 1 Pg. 145-155 (Jan 2022) ISSN: 1349-7006 [Electronic] England
PMID	34714604 (Publication Type: Journal Article)
Copyright	© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
Chemical References	Biomarkers, Tumor Cyclin E E2F1 Transcription Factor E2F1 protein, human HDGFL3 protein, human Intracellular Signaling Peptides and Proteins Histone Deacetylases
Topics	A549 Cells Animals Biomarkers, Tumor (metabolism) Cell Line, Tumor Cyclin E (metabolism) E2F1 Transcription Factor (genetics) Gene Expression Regulation, Neoplastic Histone Deacetylases (metabolism) Humans Intracellular Signaling Peptides and Proteins (metabolism) Lung Neoplasms (genetics, metabolism, pathology) Mice Neoplasm Transplantation Promoter Regions, Genetic Signal Transduction

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