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Functional analysis of HBO1 in tumor development and inhibitor screening
Ling-Li Guo1, Su-Yang Yu1, Meng Li1
1Department of Colorectal Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.
Abstract:
The aim of the present study was to explore the functions of histone acetyltransferase binding to origin recog-nition complex (ORC) 1 (HBO1) during tumor development and to screen for HBO1 inhibitors. The chromatin immuno-precipitation sequencing (ChIP-seq) data of HBO1 in the RKO human colon cancer cell line (GSE33007) were downloaded from the Gene Expression Omnibus (GEO) database. The reads were then mapped back to a reference genome hg19. The PCR duplicate reads were removed by using SAMtools software and the shift was calculated using SPP and MaSC software. The peak calling was carried out using MACS 1.4.0 software. Furthermore, the inhibitors of HBO1 were screened out from the Specs database using Dock 6.6 software. The binding sites of HBO1 were mainly distributed in the intergenic, intronic and 3'-end regions. Further analysis revealed that a total of 9,467 target genes was identified around HBO1 binding sites in the RKO cell lines and those genes mainly participated in the cell cycle, biosynthetic process, as well as other processes. Finally, 5 inhibitors with best binding affinity in the positively charged cavity of HBO1 were screened out: i) 5-[(2-hydroxybenzylidene)amino] -2-(2‑{4‑[(2‑hydroxy-benzylidene)amino]-2-sulfonatophenyl}vinyl)benzenesulfonate, ii) 3-[4-(3-bromo-4-{2-[4-(ethoxycarbonyl)anilino]-2-oxo-ethoxy}-5-methoxybenzylidene)‑3‑methyl‑5‑oxo -4,5-dihydro-1H-pyrazol-1-yl]benzoic acid, iii) 4-(4-{3-iodo‑5‑ methoxy‑4-[2-(2-methoxyanilino)-2-oxoethoxy]benzylidene}-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoic acid, iv) 5-chloro-1,3-bis{[3,5,6-trihydroxy-4-(octyloxy)tetrahydro-2H-pyran-2-yl]methyl}-1,3-dihydro-2H-benzimidazol-2-one and v) 4-{[4-(tetradecylamino)-1-naphthyl]diazenyl}benzoic acid. As a whole, in this study, we identified the possible binding sites and biological functions of HBO1. The potential inhibitors of HBO1 were also screened, which prove to be helpful for the inhibition of HBO1 during tumor development.
Insights
This study explored histone acetyltransferase binding to origin recognition complex 1 (HBO1) functions in tumor development and identified potential HBO1 inhibitors. Findings reveal HBO1
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Histone acetyltransferase binding to origin recognition complex 1 (HBO1) is implicated in cellular processes.
- Understanding HBO1's role in tumor development is crucial for therapeutic strategies.
Purpose of the Study:
- To investigate the functions of HBO1 during tumor development.
- To identify potential inhibitors of HBO1 for cancer therapy.
Main Methods:
- Chromatin immunoprecipitation sequencing (ChIP-seq) data analysis of HBO1 in colon cancer cells.
- Bioinformatic analysis to identify HBO1 target genes and binding sites.
- Molecular docking simulations to screen for HBO1 inhibitors from a chemical database.
Main Results:
- HBO1 binding sites were identified in intergenic, intronic, and 3'-end regions.
- 9,467 target genes associated with HBO1 binding were identified, primarily involved in cell cycle and biosynthesis.
- Five potential HBO1 inhibitors with significant binding affinity were screened.
Conclusions:
- This study elucidates the functional roles and binding sites of HBO1 in colon cancer cells.
- Identified HBO1 inhibitors offer potential therapeutic avenues for targeting HBO1 in tumor development.
