Genome-wide association studies have identified more than 100 common single nucleotide polymorphisms (SNPs) that are associated with prostate cancer risk. However, the vast majority of these SNPs lie in noncoding regions of the genome. To test whether these risk SNPs regulate their target genes through long-range chromatin interactions, we applied capture-based 3C sequencing technology to investigate possible cis-interactions at ten prostate cancer risk loci in six cell lines. We identified significant physical interactions between risk regions and their potential target genes including CAPG at 2p11.2, C2orf43 at 2p24.1, RFX6 at 6q22.1, NFASC at 1q32.1, MYC at 8q24.1 and AGAP7P at 10q11.23. Most of the interaction peaks were co-localized to regions of active histone modification and transcription factor binding sites. Expression quantitative trait locus (eQTL) analysis showed suggestive eQTL signals at rs1446669, rs699664 and rs1078004 for CAPG (p < 0.004), rs13394027 for C2orf43 (p = 2.25E-27), rs10993994 and rs4631830 for AGAP7P (p < 8.02E-5). Further analysis revealed an enhancer activity at genomic region surrounding rs4631830 which was expected to disrupt HOXB-like DNA binding affinity. This study identifies a set of candidate genes and their potential regulatory variants, and provides additional evidence showing the role of long-range chromatin interactions in prostate cancer etiology.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4793270 | PMC |
| http://dx.doi.org/10.1038/srep23202 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The Safety and Efficacy of Targeted Alpha Therapy, Ac-225 Prostate-Specific Membrane Antigen, in Patients With Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis.
Prostate
January 2025
Department of Urology, Istanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Istanbul, Turkey.
Background: Metastatic castration resistance prostate cancer (mCRPC) is a challenging disease with a significant burden of mortality and morbidity. Most of the patients attain resistance to the available treatments, necessitating further novel therapies in this clinical setting. Actinium 225 (Ac) prostate-specific membrane antigen (PSMA) radioligand therapy has emerged as a promising option and has been utilized for the last decade.
View Article and Find Full Text PDFNeutrophil-to-lymphocyte ratio as a prognostic factor in patients with castration-resistant prostate cancer treated with docetaxel-based chemotherapy: a meta-analysis.
BMC Urol
January 2025
The School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian Province, 350122, China.
Background: In recent years, many studies have illustrated that the neutrophil-to-lymphocyte ratio (NLR) is a prognostic factor of metastatic castration-resistant prostate cancer (mCRPC), but their conclusions are controversial. The aim of this study was to assess the prognostic value of the NLR in patients with mCRPC treated with docetaxel-based chemotherapy.
Methods: Database searches were conducted in PubMed, EMBASE and the Cochrane Library to retrieve relevant published English-language literature up to 20 February 2023.
PSMA PET/CT based multimodal deep learning model for accurate prediction of pelvic lymph-node metastases in prostate cancer patients identified as candidates for extended pelvic lymph node dissection by preoperative nomograms.
Eur J Nucl Med Mol Imaging
January 2025
Department of Nuclear Medicine, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, P.R. China.
Purpose: To develop and validate a prostate-specific membrane antigen (PSMA) PET/CT based multimodal deep learning model for predicting pathological lymph node invasion (LNI) in prostate cancer (PCa) patients identified as candidates for extended pelvic lymph node dissection (ePLND) by preoperative nomograms.
Methods: [Ga]Ga-PSMA-617 PET/CT scan of 116 eligible PCa patients (82 in the training cohort and 34 in the test cohort) who underwent radical prostatectomy with ePLND were analyzed in our study. The Med3D deep learning network was utilized to extract discriminative features from the entire prostate volume of interest on the PET/CT images.
p53-loss induced prostatic epithelial cell plasticity and invasion is driven by a crosstalk with the tumor microenvironment.
Cell Death Dis
January 2025
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.
Prostate cancer is a heterogeneous disease with a slow progression and a highly variable clinical outcome. The tumor suppressor genes PTEN and TP53 are frequently mutated in prostate cancer and are predictive of early metastatic dissemination and unfavorable patient outcomes. The progression of solid tumors to metastasis is often associated with increased cell plasticity, but the complex events underlying TP53-loss-induced disease aggressiveness remain incompletely understood.
View Article and Find Full Text PDFActivation of P38 MAPK Signaling Cascade is Linked with Clinical Outcomes and Therapeutic Responses in Human Cancers.
Biochemistry (Mosc)
December 2024
Moscow Institute of Physics and Technology, Dolgoprudny, 141701, Russia.
Activation of the p38 mitogen-activated protein kinase (MAPK) pathways is vital in regulating cell growth, differentiation, apoptosis, and stress response, significantly affecting tumorigenesis and cancer progression. We developed a bioinformatic technique to construct an interactome network-based molecular pathways for genes of interest and quantify their activation levels using high-throughput gene expression data. This study is focused on the p38α, p38β, p38γ, and p38δ kinases, examining their activation levels (PALs) based on transcriptomic data and their associations with survival and drug responsiveness across various cancer types.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!