Identification of endonuclease domain-containing 1 as a novel tumor suppressor in prostate cancer

Abstract

BackgroundEndonuclease domain containing 1 (ENDOD1) is implicated in tumorigenesis and aggressiveness of multiple tumors. In this study, we aimed to investigate the role of ENDOD1 in prostate cancer (PCa).MethodsImmunohistochemistry were performed in 30 cases of benign prostatic hyperplasia (BPH) and 50 cases of PCa to identify its association with clinicopathological characteristics. Real-time PCR and western blot were used to detect ENDOD1 mRNA and protein expression in normal prostatic epithelial and PCa cell lines. MTT assays were employed to determine the effect of cell proliferation. Flow cytometry was used to explore the cell cycle distribution and apoptotic effects. Transwell migration and invasion assays were done to evaluate changes in the ability of cell migration and invasion.ResultsImmunoreactivity scores of ENDOD1 showed no statistical difference between BPH and low-grade PCa, whereas lower immunostaining scores were observed in high-grade compared with low-grade PCa. Real-time PCR data indicated that ENDOD1 mRNA expression was markedly increased in LNCaP and 22Rv1 cells and decreased in PC3 and DU145 cells compared to the normal epithelial cells RWPE1. Western blot showed that androgen-sensitive LNCaP cells had the highest protein expression level of ENDOD1, whereas castration-resistant PCa cell lines PC3 and DU145 had significantly lower protein levels. Meanwhile, overexpression of ENDOD1 suppressed cell proliferation, induced G0/G1 cell cycle arrest and inhibited cell migration and invasion. Conversely, siRNA-mediated silencing of ENDOD1 promoted cell proliferation, migration and invasion. No apoptotic effects occurred upon manipulation of ENDOD1 expression.ConclusionOur results indicate that ENDOD1 is a novel tumor suppressor in PCa, which may be employed as a new drug target of preventing progression to metastatic castration-resistant prostate cancer.

Immunomagnetic-Enriched Subpopulations of Melanoma Circulating Tumour Cells (CTCs) Exhibit Distinct Transcriptome Profiles

“…With regard to the genes specifically up-regulated in the MCSP CTC fraction, the majority have been involved in metastasis ( LOXL4, ST6GALNAC2, PYGL) , tumour growth ( PLK2 , CYSTM1, GLUL ), and/or melanoma biology ( SEC31A, WIPI1 , SKP1 ) [42,43,45,46,47,48,49,50,51,52,53]. Similarly, the up-regulated genes in the ABCB5 CTC fractions were involved in metastasis ( CALU , CYB5R1, DUSP3, CREG1, ENDOD1 ), tumour growth, and/or melanoma biology ( H1F0, SCNA, WIPI1, TXN2 ) [42,43,54,55,56,57,58,59,60]. These findings support the suggestion that these two CTC subpopulations exhibit different gene expression patterns but similar molecular mechanisms underlying their biology.…”

Predicting response to enzalutamide and abiraterone in metastatic prostate cancer using whole-omics machine learning

“…Within the DEGs ( n = 151), we observed uniform presence of genes regulating or attributed to epithelial-mesenchymal transition (EMT) such as TIMP-3 and TGFBI , or found genes previously attributed to tumorigenesis, poor survival and/or aggressiveness such as RGS2 and SLC7A5 to harbor higher expression within the poor responders vs. the good responders 31 , 32 . Conversely, genes attributed to the suppression of tumor growth and/or metastatic potential such as RBM47 and ENDOD1 were expressed in fewer quantity 33 , 34 (Suppl. Fig.…”

A novel DNA methylation signature to improve survival prediction of progression-free survival for testicular germ cell tumors

“…PANX1 encodes a protein involved in intercellular communication, and mutations of this gene are associated with an increased expression of molecules involved in cancer growth 34 . ENDOD1 encodes a protein that is implicated in cell death, and is found at elevated levels in certain types of cancer 35 . MAF is a gene involved www.nature.com/scientificreports/ in cell proliferation and has been observed to be mutated frequently in various types of cancer 36 .…”