ZFP91—A Newly Described Gene Potentially Involved in Prostate Pathology

Abstract

In search for novel molecular targets in benign prostate hyperplasia (BPH), a PCR Array based screening of 84 genes was performed. Of those, expression of ZFP91 (ZFP91 zinc finger protein) was notably upregulated. Limited data concerning the function of ZFP91 product show that it is a potential transcription factor upregulated in human acute myelogenous leukemia and most recently found to be the non-canonical NF-κB pathway regulator. In order to test this finding on a larger number of samples, prostate specimens were obtained from patients undergoing adenomectomy for BPH (n = 21), and as a control, from patients undergoing radical cystectomy for bladder cancer (prostates unchanged pathologically, n = 18). Similar studies were performed on cultured human prostate cancer cell lines: LNCaP, DU145, 22Rv1, PC-3; as well as normal prostate epithelial cells—PrEC. Methods employed included: Human Obesity PCR Array (Qiagen), QPCR and Western blotting. QPCR studies confirmed significant overexpression of ZFP91 in BPH samples. On a protein level, however, comparison between normal and BPH prostates revealed insignificant differences. As for prostate cell lines examined, all expressed ZFP91 mRNA. Western blotting analysis showed markedly higher protein levels of ZFP91 in all cancer cell lines in comparison with normal (PrEC) cells. In conclusion, the upregulated ZFP91 mRNA in BPH, not accompanied by parallel changes in ZFP91 protein levels, together with ZFP91 protein abundance in prostate cancer cell lines suggest ZFP91 involvement in these prostate diseases.

ZFP91: A Noncanonical NF-κB Signaling Pathway Regulator with Oncogenic Properties Is Overexpressed in Prostate Cancer

“…Analyses were performed as described earlier [2, 18, 19]. Briefly, primers were designed by Primer 3 software (Whitehead Institute for Biomedical Research, Cambridge, USA) and purchased from the Laboratory of DNA Sequencing and Oligonucleotide Synthesis (Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland).…”

“…Still novel targets are being searched to aid in diagnosis and treatment of this complex and heterogeneous disease [1]. In 2014 our team described changes in expression of little-studied ZFP91 zinc finger protein gene ( ZFP91 ) in benign prostate hyperplasia (BPH) and in prostate cancer cell lines [2]. Recently found oncogenic properties of this gene prompted us to further study its significance in prostate cancer pathogenesis.…”

Zinc finger protein 91 (ZFP91) activates HIF-1α via NF-κB/p65 to promote proliferation and tumorigenesis of colon cancer

“…It has been reported that ZFP91 interacts with ARF tumor suppressor (cyclin-dependent kinase inhibitor 2A), which is known for its induction of p53-dependent cell death or growth arrest in response to activated oncogenes [2]. Furthermore, ZFP91 plays a critical role in acute myelogenous leukemia and prostate pathology [3, 4]. Our previous study indicated that ZFP91 is an atypical E3 ligase activating NF-κB-inducing kinase (NIK) via Lys 63 -linked ubiquitination in the noncanonical NF-κB signaling pathway [5, 6].…”

Lack of expression of preproorexin and orexin receptors genes in human normal and prostate cancer cell lines

“…To validate the obtained results in an another manner, we used commercially available primers, which, however, yielded false positive results: with 'PPH01112A for human HCRTR1' primer, reaction products of the size of approximately 100 bp were observed in all studied human prostatic cell lines as well as in negative controls (-RT). Therefore, we are not surprised by results obtained by means of Human Obesity RT2 Profiler PCR Array (SuperArrayBioscience; SABioscience) applied by us in studies on OXR1 expression in normal human prostate and benign prostate hyperplasia [29]. In these studies we demonstrated reaction products for OXR1; however, the primers applied were the same, as purchased for the present study.…”

“…On the other hand, in our earlier QPCR study we were unable to demonstrate expression of ppOX in human normal and hyperplastic prostate [16]. Likewise, in our recent microarray study (Human Obesity RT2 Profiler PCR Array, Qiagen) we were unable to demonstrate expression of ppOX in both normal human prostate gland and benign prostate hyperplasia [29].…”