RNA-Binding Motif 3 Protein Expression and Nuclear Architecture Changes as a Combined Biomarker to Predict Aggressive and Recurrent Prostate Cancer.

2017 ◽  
Vol 3 (1) ◽  
pp. 192-203
Author(s):  
Neil Carleton ◽  
◽  
Guangjing Zhu ◽  
M. Craig Miller ◽  
Christine Davis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Protein Expression ◽  
Rna Binding ◽  
Nuclear Architecture ◽  
Binding Motif ◽  
Recurrent Prostate Cancer

scholarly journals Characterization of RNA‐binding motif 3 (RBM3) protein levels and nuclear architecture changes in aggressive and recurrent prostate cancer

2020 ◽  
Vol 3 (3) ◽  
Author(s):  
Neil M. Carleton ◽  
Guangjing Zhu ◽  
M. Craig Miller ◽  
Christine Davis ◽  
Prakash Kulkarni ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Rna Binding ◽  
Nuclear Architecture ◽  
Binding Motif ◽  
Recurrent Prostate Cancer ◽  
Protein Levels

A translational effort to identify prognostic and predictive biomarkers in pancreatic cancer among RBM3-regulated genes.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 305-305
Author(s):  
Sofie Olsson Hau ◽  
Emelie Karnevi ◽  
Sebastian Lundgren ◽  
Bo Li ◽  
Seodhna Lynch ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Protein Expression ◽  
Rna Binding ◽  
Predictive Biomarkers ◽  
Gene Set Enrichment Analysis ◽  
Binding Motif ◽  
Potential Utility ◽  
Dismal Prognosis ◽  
Response To Chemotherapy

305 Background: Pancreatic cancer has a dismal prognosis and clinical protocols are still lacking predictive biomarkers. RNA-binding motif protein 3 (RBM3) has emerged as a promising biomarker in several solid cancers, including pancreatic cancer. High RBM3 expression in human tumors has been associated with good response to chemotherapy, as well as to confer increased chemosensitivity in vitro. The aim of this study was to identify RBM3-regulated genes in pancreatic cells in vitro, and further interrogate their potential utility as prognostic and predictive biomarkers in a translational setting. Methods: Next generation RNA-sequencing was applied to compare gene expression between MIAPaCa-2 cells with siRNA-downregulated RBM3 and control cells. Single genes with the strongest association to RBM3 were further selected by gene set enrichment analysis, and their prognostic value in pancreatic cancer was examined in The Cancer Genome Atlas (TCGA). The most promising biomarker candidates with well-validated antibodies were then analyzed by immunohistochemistry in tissue microarrays with tumors from a consecutive, retrospective cohort of 175 patients with periampullary and pancreatic adenocarcinoma. Results: MIAPaCa-2 cells with downregulated RBM3 displayed 21 differentially expressed genes (p < 0.01). One of the top downregulated genes was PDS cohesion associated factor A (PDS5A) encoding a protein involved in sister chromatid cohesion. PDS5A protein expression was reduced in siRBM3-treated MIAPaCa-2 cells compared to control cells. High PDS5A mRNA expression was significantly associated with a reduced survival in pancreatic cancer in the TCGA (n = 176, p = 0.026). High PDS5A protein expression in the separate cohort was significantly associated with a poor prognosis but predictive of improved response to adjuvant chemotherapy in KRAS-mutated, but not wild-type, pancreatobiliary-type tumors (p for interaction = 0.043). Conclusions: Here, we provide the first report of the expression of PDS5A in pancreatic and periampullary cancer, suggesting its potential utility as a prognostic and predictive biomarker. Further studies to unravel the underlying mechanisms are encouraged.

Androgen Receptor Gene Amplification and Protein Expression in Recurrent Prostate Cancer

2003 ◽  
Vol 170 (5) ◽  
pp. 1817-1821 ◽  
Author(s):  
O. HARRIS FORD ◽  
CHRISTOPHER W. GREGORY ◽  
DESOK KIM ◽  
ANDREW B. SMITHERMAN ◽  
JAMES L. MOHLER
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Protein Expression ◽  
Gene Amplification ◽  
Receptor Gene ◽  
Androgen Receptor Gene ◽  
Recurrent Prostate Cancer

scholarly journals PUM1 represses CDKN1B translation and contributes to prostate cancer progression

2021 ◽  
Author(s):  
Eugene Yujun Xu
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Protein Expression ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Translational Control ◽  
Rna Binding ◽  
Prostate Cancer Cell ◽  
Mrna Level ◽  
Critical Role

Posttranscriptional regulation of cancer gene expression programs plays a vital role in carcinogenesis; identifying the critical regulators of tumorigenesis and their molecular targets may provide novel strategies for cancer diagnosis and therapeutics. Highly conserved RNA binding protein PUM1 regulates mouse growth and cell proliferation, propelling us to examine its role in cancer. We found human PUM1 is highly expressed in a diverse group of cancer, including prostate cancer; enhanced PUM1 expression is also correlated with reduced survival among prostate cancer patients. Detailed expression analysis in twenty prostate cancer tissues showed enhanced expression of PUM1 at mRNA and protein levels. Knockdown of PUM1 reduced prostate cancer cell proliferation and colony formation, and subcutaneous injection of PUM1 knockdown cells led to reduced tumor size. Downregulation of PUM1 in prostate cancer cells consistently elevated CDKN1B protein expression through increased translation but did not impact its mRNA level, while overexpression of PUM1 reduced CDKN1B protein level. Our finding established a critical role of PUM1 mediated translational control, particularly the PUM1-CDKN1B axis, in prostate cancer cell growth and tumorigenesis. We proposed that PUM1-CDKN1B regulatory axis may represent a novel mechanism for the loss of CDKN1B protein expression in diverse cancers and could be potential targets for therapeutics development.

scholarly journals Decreased RNA-binding motif 5 expression is associated with tumor progression in gastric cancer

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769454 ◽  
Author(s):  
Takahiko Kobayashi ◽  
Junich Ishida ◽  
Yuichi Shimizu ◽  
Hiroshi Kawakami ◽  
Goki Suda ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Growth ◽  
Tumor Suppressor ◽  
Protein Expression ◽  
Cancer Cells ◽  
Rna Binding ◽  
Suppressor Gene ◽  
Binding Motif ◽  
Gastric Cancer Cells ◽  
Rna Binding Motif 5

RNA-binding motif 5 is a putative tumor suppressor gene that modulates cell cycle arrest and apoptosis. We recently demonstrated that RNA-binding motif 5 inhibits cell growth through the p53 pathway. This study evaluated the clinical significance of RNA-binding motif 5 expression in gastric cancer and the effects of altered RNA-binding motif 5 expression on cancer biology in gastric cancer cells. RNA-binding motif 5 protein expression was evaluated by immunohistochemistry using the surgical specimens of 106 patients with gastric cancer. We analyzed the relationships of RNA-binding motif 5 expression with clinicopathological parameters and patient prognosis. We further explored the effects of RNA-binding motif 5 downregulation with short hairpin RNA on cell growth and p53 signaling in MKN45 gastric cancer cells. Immunohistochemistry revealed that RNA-binding motif 5 expression was decreased in 29 of 106 (27.4%) gastric cancer specimens. Decreased RNA-binding motif 5 expression was correlated with histological differentiation, depth of tumor infiltration, nodal metastasis, tumor–node–metastasis stage, and prognosis. RNA-binding motif 5 silencing enhanced gastric cancer cell proliferation and decreased p53 transcriptional activity in reporter gene assays. Conversely, restoration of RNA-binding motif 5 expression suppressed cell growth and recovered p53 transactivation in RNA-binding motif 5–silenced cells. Furthermore, RNA-binding motif 5 silencing reduced the messenger RNA and protein expression of the p53 target gene p21. Our results suggest that RNA-binding motif 5 downregulation is involved in gastric cancer progression and that RNA-binding motif 5 behaves as a tumor suppressor gene in gastric cancer.

High RNA-binding motif protein 3 expression is an independent prognostic marker in operated prostate cancer and tightly linked to ERG activation and PTEN deletions

2014 ◽  
Vol 50 (4) ◽  
pp. 852-861 ◽  
Author(s):  
Katharina Grupp ◽  
Julia Wilking ◽  
Kristina Prien ◽  
Claudia Hube-Magg ◽  
Hüseyin Sirma ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Marker ◽  
Rna Binding ◽  
Binding Motif ◽  
Independent Prognostic Marker

scholarly journals The RNA-binding protein hnRNPA2 regulates β-catenin protein expression and is overexpressed in prostate cancer

RNA Biology ◽  
2014 ◽  
Vol 11 (6) ◽  
pp. 755-765 ◽  
Author(s):  
Jacqueline Stockley ◽  
M Eugenia M Villasevil ◽  
Colin Nixon ◽  
Imran Ahmad ◽  
Hing Y Leung ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Protein Expression ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein

scholarly journals Targeting the Lnc-OPHN1-5/androgen receptor/hnRNPA1 complex increases Enzalutamide sensitivity to better suppress prostate cancer progression

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Meng Zhang ◽  
Yin Sun ◽  
Chi-Ping Huang ◽  
Jie Luo ◽  
Li Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Protein Expression ◽  
Cancer Progression ◽  
Translational Control ◽  
Rna Binding ◽  
Formation Rate ◽  
Tumor Formation ◽  
Clinical Samples ◽  
Control Group

AbstractLong non-coding RNAs (lncRNAs) have been found to play critical roles in regulating gene expression, but their function in translational control is poorly understood. We found lnc-OPHN1-5, which lies close to the androgen receptor (AR) gene on chromosome X, increased prostate cancer (PCa) Enzalutamide (Enz) sensitivity via decreasing AR protein expression and associated activity. Mechanism dissection revealed that lnc-OPHN1-5 interacted with AR-mRNA to minimize its interaction with the RNA binding protein (RBP) hnRNPA1. Suppressing lnc-OPHN1-5 expression promoted the interaction between AR-mRNA and hnRNPA1, followed by an increase of ribosome association with AR-mRNA and translation. This effect was reversed by increasing lnc-OPHN1-5 expression. Consistently, the in vivo mice model confirmed that knocking down lnc-OPHN1-5 expression in tumors significantly increased the tumor formation rate and AR protein expression compared with the control group. Furthermore, knocking down hnRNPA1 blocked/reversed shlnc-OPHN1-5-increased AR protein expression and re-sensitized cells to Enz treatment efficacy. Evidence from Enz-resistant cell lines, patient-derived xenograft (PDX) models, clinical samples, and a human PCa study accordantly suggested that patients with low expression of lnc-OPHN1-5 likely have unfavorable prognoses and probably are less sensitive to Enz treatment. In summary, targeting this newly identified lnc-OPHN1-5/AR/hnRNPA1 complex may help develop novel therapies to increase Enz treatment sensitivity for suppressing the PCa at an advanced stage.

scholarly journals RNA-binding protein DDX3 mediates posttranscriptional regulation of androgen receptor: A mechanism of castration resistance

2020 ◽  
Vol 117 (45) ◽  
pp. 28092-28101 ◽  
Author(s):  
Jordan E. Vellky ◽  
Sean T. McSweeney ◽  
Emily A. Ricke ◽  
William A. Ricke
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Protein Expression ◽  
Messenger Rna ◽  
Posttranscriptional Regulation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Protein Translation

Prostate cancer (CaP) driven by androgen receptor (AR) is treated with androgen deprivation; however, therapy failure results in lethal castration-resistant prostate cancer (CRPC). AR-low/negative (ARL/−) CRPC subtypes have recently been characterized and cannot be targeted by hormonal therapies, resulting in poor prognosis. RNA-binding protein (RBP)/helicase DDX3 (DEAD-box helicase 3 X-linked) is a key component of stress granules (SG) and is postulated to affect protein translation. Here, we investigated DDX3-mediated posttranscriptional regulation of AR mRNA (messenger RNA) in CRPC. Using patient samples and preclinical models, we objectively quantified DDX3 and AR expression in ARL/− CRPC. We utilized CRPC models to identify DDX3:AR mRNA complexes by RNA immunoprecipitation, assess the effects of DDX3 gain/loss-of-function on AR expression and signaling, and address clinical implications of targeting DDX3 by assessing sensitivity to AR-signaling inhibitors (ARSI) in CRPC xenografts in vivo. ARL/− CRPC expressed abundant AR mRNA despite diminished levels of AR protein. DDX3 protein was highly expressed in ARL/− CRPC, where it bound to AR mRNA. Consistent with a repressive regulatory role, DDX3 localized to cytoplasmic puncta with SG marker PABP1 in CRPC. While induction of DDX3-nucleated SGs resulted in decreased AR protein expression, inhibiting DDX3 was sufficient to restore 1) AR protein expression, 2) AR signaling, and 3) sensitivity to ARSI in vitro and in vivo. Our findings implicate the RBP protein DDX3 as a mechanism of posttranscriptional regulation for AR in CRPC. Clinically, DDX3 may be targetable for sensitizing ARL/− CRPC to AR-directed therapies.

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