Ribosome-binding protein-1 (RRBP1) expression in prostate carcinomas and its relationship with clinicopathological prognostic factors.

INTRODUCTION: Studies in recent years have shown that ribosome-binding protein-1 (RRBP1) is expressed at high rates in many cancers and that it may be a potential prognostic biomarker. The objective of the present study is to determine the RRBP1 expression level in prostatic carcinoma and neighboring non-neoplastic prostate tissue, the relationship between its expression level with prognostic factors, and the role of RRBP1 in the development of prostate cancer. MATERIALS AND METHODS: The study included 45 patients who were diagnosed with prostatic carcinoma and underwent radical prostatectomy in our center between the years 2010 and 2021. Pathology reports were reviewed. Mann-Whitney U test was used for the comparison of RRBP1 and GADPH values of the cases (control and tumoral tissue) between the primary tumor stage (pT) and Gleason score (GS) groups. Hierarchical regression analysis was used to explain the effective variables in explaining the RRBP1 value of the research cases. RESULTS: According to the Mann-Whitney U test, mean and median RRBP1-T values of the cases with GS ≥ 8 were detected to be statistically significantly higher than the mean and median RRBP1-T values of the cases with GS < 8. CONCLUSION: We found out that RRBP1 was expressed at higher rates in patients with high GS and advanced-stage patients. This result indicated that RRBP1 expression may be important in predicting the prognosis of prostate carcinoma.

ER ribosomal-binding protein 1 regulates blood pressure and potassium homeostasis by modulating intracellular renin trafficking.

BACKGROUND: Genome-wide association studies (GWASs) have linked RRBP1 (ribosomal-binding protein 1) genetic variants to atherosclerotic cardiovascular diseases and serum lipoprotein levels. However, how RRBP1 regulates blood pressure is unknown. METHODS: To identify genetic variants associated with blood pressure, we performed a genome-wide linkage analysis with regional fine mapping in the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) cohort. We further investigated the role of the RRBP1 gene using a transgenic mouse model and a human cell model. RESULTS: In the SAPPHIRe cohort, we discovered that genetic variants of the RRBP1 gene were associated with blood pressure variation, which was confirmed by other GWASs for blood pressure. Rrbp1- knockout (KO) mice had lower blood pressure and were more likely to die suddenly from severe hyperkalemia caused by phenotypically hyporeninemic hypoaldosteronism than wild-type controls. The survival of Rrbp1-KO mice significantly decreased under high potassium intake due to lethal hyperkalemia-induced arrhythmia and persistent hypoaldosteronism, which could be rescued by fludrocortisone. An immunohistochemical study revealed renin accumulation in the juxtaglomerular cells of Rrbp1-KO mice. In the RRBP1-knockdown Calu-6 cells, a human renin-producing cell line, transmission electron and confocal microscopy revealed that renin was primarily retained in the endoplasmic reticulum and was unable to efficiently target the Golgi apparatus for secretion. CONCLUSIONS: RRBP1 deficiency in mice caused hyporeninemic hypoaldosteronism, resulting in lower blood pressure, severe hyperkalemia, and sudden cardiac death. In juxtaglomerular cells, deficiency of RRBP1 reduced renin intracellular trafficking from ER to Golgi apparatus. RRBP1 is a brand-new regulator of blood pressure and potassium homeostasis discovered in this study.

Analysis of the association of ANO3/MUC15, COL4A4, RRBP1, and KLK1 polymorphisms with COPD susceptibility in the Kashi population.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a complex, multifactorial, polygenic disease. The rate of occurrence of COPD in the Kashi population (Uyghur) is significantly higher than that observed nationwide. The identification of COPD-related genes in the Chinese Uyghur population could provide useful insights that could help us understand this phenomenon. Our previous whole-exome sequencing study of three Uyghur families with COPD demonstrated that 72 mutations in 55 genes might be associated with COPD; these included rs15783G > A in the anoctamin 3 (ANO3) gene/mucin 15 (MUC15) gene, rs1800517G > A in the collagen type IV alpha 4 chain (COL4A4) gene, rs11960G > A in the ribosome binding protein 1 (RRBP1) gene, and rs5516C > G in the kallikrein 1 (KLK1) gene. This case-control study aimed to further validate the association of the four mutations with COPD in the Chinese Uyghur population. METHODS: Sanger sequencing was used for the genotyping of four polymorphisms (ANO3/MUC15 rs15783, COL4A4 rs1800517, RRBP1 rs11960, and KLK1 rs5516) in 541 unrelated Uyghur COPD patients and 534 Uyghur healthy controls. We then conducted stratified analyses based on the smoking status and airflow limitation severity, to explore the correlation between selected gene polymorphisms and COPD. RESULTS: ANO3/MUC15 rs15783 and KLK1 rs5516 polymorphisms could significantly reduce COPD risk (p < 0.05), but COL4A4 rs1800517 and RRBP1 rs11960 polymorphisms were not correlated with COPD in the entire population. In a stratified analysis of smoking status, non-smokers with the ANO3/MUC15 rs15783G/G genotype (OR = 0.63, p = 0.032) or COL4A4 rs1800517 allele G (OR = 0.80, p = 0.023) had a reduced risk of COPD. Smokers with the RRBP1 rs11960A/G genotype had a lower risk of COPD (OR = 0.41, p = 0.025). The KLK1 rs5516G > C polymorphism was associated with a decreased risk of COPD (OR < 1, p < 0.05), irrespective of the smoking status of individuals. No significant association with COPD severity was observed in individuals with these four polymorphisms (p > 0.05). CONCLUSION: We identified four previously unreported mutations (ANO3/MUC15 rs15783, COL4A4 rs1800517, RRBP1 rs11960, and KLK1 rs5516) that might decrease the COPD risk in individuals with different smoking statuses in the Chinese Uyghur population. Our findings provide new light for the genetic risk factors associated with the occurrence of COPD.

Hypomethylated RRBP1 Potentiates Tumor Malignancy and Chemoresistance in Upper Tract Urothelial Carcinoma.

Ribosome-binding protein 1 (RRBP1) is a potential oncogene in several cancer types. However, the correlation between RRBP1 expression and the prognosis of patients with upper tract urothelial carcinoma (UTUC) remains unclear. In this study, we identified that RRBP1 is associated with carcinogenesis and metastasis in UTUC using a methylation profiling microarray. High correlations between RRBP1 and cancer stages, nodal metastasis status, molecular subtypes, and prognosis in bladder urothelial cancer (BLCA) were found. Aberrant DNA methylation in the gene body region of RRBP1 was determined in UTUC tissues by methylation-specific PCR. RRBP1 expression was significantly increased in UTUC tissues and cell lines, as determined by real-time PCR and immunohistochemistry. RRBP1 depletion significantly reduced BFTC909 cell growth induced by specific shRNA. On the other hand, molecular subtype analysis showed that the expression of RRBP1 was associated with genes related to cell proliferation, epithelial-mesenchymal transition, and basal markers. A patient-derived organoid model was established to analyze patients' responses to different drugs. The expression of RRBP1 was related to chemoresistance. Taken together, these results provide the first evidence that RRBP1 gene body hypomethylation predicts RRBP1 high expression in UTUC. The data highlight the importance of RRBP1 in UTUC malignancy and chemotherapeutic tolerance.

ALK oncoproteins in atypical inflammatory myofibroblastic tumours: novel RRBP1-ALK fusions in epithelioid inflammatory myofibroblastic sarcoma.

ALK oncogenic activation mechanisms were characterized in four conventional spindle-cell inflammatory myofibroblastic tumours (IMT) and five atypical IMT, each of which had ALK genomic perturbations. Constitutively activated ALK oncoproteins were purified by ALK immunoprecipitation and electrophoresis, and were characterized by mass spectrometry. The four conventional IMT had TPM3/4-ALK fusions (two cases) or DCTN1-ALK fusions (two cases), whereas two atypical spindle-cell IMT had TFG-ALK and TPM3-ALK fusion in one case each, and three epithelioid inflammatory myofibroblastic sarcomas had RANBP2-ALK fusions in two cases, and a novel RRBP1-ALK fusion in one case. The epithelioid inflammatory myofibroblastic sarcoma with RRBP1-ALK fusion had cytoplasmic ALK expression with perinuclear accentuation, different from the nuclear membranous ALK localization in epithelioid inflammatory myofibroblastic sarcomas with RANBP2-ALK fusions. Evaluation of three additional uncharacterized epithelioid inflammatory myofibroblastic sarcomas with ALK cytoplasmic/perinuclear- accentuation expression demonstrated RRBP1-ALK fusion in two cases. These studies show that atypical spindle-cell IMT can utilize the same ALK fusion mechanisms described previously in conventional IMT, whereas in clinically aggressive epithelioid inflammatory myofibroblastic sarcoma we identify a novel recurrent ALK oncogenic mechanism, resulting from fusion with the RRBP1 gene. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

La Autoantigen Induces Ribosome Binding Protein 1 (RRBP1) Expression through Internal Ribosome Entry Site (IRES)-Mediated Translation during Cellular Stress Condition.

The function of ribosome binding protein 1 (RRBP1) is regulating the transportation and secretion of some intracellular proteins in mammalian cells. Transcription of RRBP1 is induced by various cytokines. However, few studies focused on the process of RRPB1 mRNA translation. The RRBP1 mRNA has a long 5' untranslated region that potentially formed a stable secondary structure. In this study, we show that the 5' UTR of RRBP1 mRNA contains an internal ribosome entry site (IRES). Moreover, the RRBP1 expression is induced by chemotherapeutic drug paclitaxel or adriamycin in human hepatocellular carcinoma cells and accompanied with the increased expression of La autoantigen (La), which binds to RRBP1 IRES element and facilitates translation initiation. Interestingly, we found IRES-mediated RRBP1 translation is also activated during serum-starvation condition which can induce cytoplasmic localization of La. After mapping the entire RRBP1 5' UTR, we determine the core IRES activity is located between nt-237 and -58. Furthermore, two apical GARR loops within the functional RRBP1 IRES elements may be important for La binding. These results strongly suggest an important role for IRES-dependent translation of RRBP1 mRNA in hepatocellular carcinoma cells during cellular stress conditions.

Expression of ribosome-binding protein 1 correlates with shorter survival in Her-2 positive breast cancer.

The aim of this study is to investigate the expression of ribosome-binding protein 1 (RRBP1) in invasive breast cancer and to analyze its relationship to clinical features and prognosis. RRBP1 expression was studied using real-time quantitative PCR and western blotting using pair-matched breast samples and immunohistochemical staining using a tissue microarray. Then the correlation between RRBP1 expression and clinicopathologic features was analyzed. RRBP1 mRNA and protein expression were significantly increased in breast cancer tissues compared with normal tissues. The protein level of RRBP1 is proved to be positively related to histological grade (P = 0.02), molecular subtype (P = 0.048) and status of Her-2 (P = 0.026) and P53 (P = 0.015). We performed a grade-stratified analysis of all patients according to the level of RRBP1 expression and found that RRBP1 overexpression highly affected overall survival in patients with early-stage (I and II) tumors (P = 0.042). Furthermore, Her-2 positive patients with negative RRBP1 expression had longer overall survival rates than those with positive RRBP1 expression (P = 0.031). Using multivariate analysis, it was determined that lymph node metastasis (LNM, P = 0.002) and RRBP1 expression (P = 0.005) were independent prognosis factors for overall survival. RRBP1 is a valuable prognostic factor in Her-2-positive breast cancer patients, indicating that RRBP1 is a potentially important target for the prediction of prognosis.

Axonal endoplasmic reticulum tubules control local translation via P180/RRBP1-mediated ribosome interactions.

Local mRNA translation in axons is critical for the spatiotemporal regulation of the axonal proteome. A wide variety of mRNAs are localized and translated in axons; however, how protein synthesis is regulated at specific subcellular sites in axons remains unclear. Here, we establish that the axonal endoplasmic reticulum (ER) supports axonal translation in developing rat hippocampal cultured neurons. Axonal ER tubule disruption impairs local translation and ribosome distribution. Using nanoscale resolution imaging, we find that ribosomes make frequent contacts with axonal ER tubules in a translation-dependent manner and are influenced by specific extrinsic cues. We identify P180/RRBP1 as an axonally distributed ribosome receptor that regulates local translation and binds to mRNAs enriched for axonal membrane proteins. Importantly, the impairment of axonal ER-ribosome interactions causes defects in axon morphology. Our results establish a role for the axonal ER in dynamically localizing mRNA translation, which is important for proper neuron development.

Expression of Synj2bp in mouse liver regulates the extent of wrappER-mitochondria contact to maintain hepatic lipid homeostasis.

BACKGROUND: In mouse liver hepatocytes, nearly half of the surface area of every mitochondrion is covered by wrappER, a wrapping-type of ER that is rich in fatty acids and synthesizes lipoproteins (VLDL) (Anastasia et al. in Cell Rep 34:108873, 2021; Hurtley in Science (80- ) 372:142-143, 2021; Ilacqua et al. in J Cell Sci 135:1-11, 2021). A disruption of the ultrastructure of the wrappER-mitochondria contact results in altered fatty acid flux, leading to hepatic dyslipidemia (Anastasia et al. 2021). The molecular mechanism that regulates the extent of wrappER-mitochondria contacts is unknown. METHODS: We evaluated the expression level of the mitochondrial protein Synj2bp in the liver of normal and obese (ob/ob) mice. In addition, we silenced its expression in the liver using an AAV8 vector. We coupled quantitative EM morphometric analysis to proteomics and lipid analyses on these livers. RESULTS: The expression level of Synj2bp in the liver positively correlates with the extent of wrappER-mitochondria contacts. A 50% reduction in wrappER-mitochondria contacts causes hepatic dyslipidemia, characterized by a gross accumulation of lipid droplets in the liver, an increased hepatic secretion of VLDL and triglycerides, a curtailed ApoE expression, and an increased capacity of mitochondrial fatty acid respiration. CONCLUSION: Synj2bp regulates the extent of wrappER-mitochondria contacts in the liver, thus contributing to the control of hepatic lipid flux.

A recurrent inflammatory myofibroblastic tumor patient with two novel ALK fusions: a case report.

Background: Inflammatory myofibroblastic tumor (IMT) is a rare disease that mainly involves the lung and the abdomen. The gold standard of the IMT treatment is radical surgery, while chemotherapy and radiotherapy are represented usually for unresectable lesions. Anaplastic lymphoma kinase (ALK) rearrangements are present in approximately 50% of IMT patients, and several clinical trials of ALK tyrosine kinase inhibitors (TKIs) in the treatment of ALK-positive IMT patients are underway. Case Description: We reported a case of IMT in the right pelvic cavity. Initially, the patient underwent resection of multiple lesions. Unfortunately, the patient's tumor recurred half a year later, and enhanced computerized tomography (CT) of the whole abdomen revealed multiple low-density masses. Then the patient underwent resection of the recurrent tumors. Immunohistochemical staining exhibited the expression of ALK in the tumor cells, and next-generation sequencing (NGS) technology revealed two novel ALK fusions, ALK-ribosome binding protein 1 (RRBP1) and hydroxyacid oxidase 1 (HAO1)-ALK fusions. These fusions were able to be transcribed and captured by RNA level. And the two fusions have not been reported in the IMTs. Conclusions: This case expanded the range of ALK fusion types and provided a promising molecular-targeted treatment strategy. In addition, the two novel ALK fusions may be the recurrent oncogenic mechanism in clinically aggressive IMT.

RRBP1 depletion of bone metastatic cancer cells contributes to enhanced expression of the osteoblastic phenotype.

Bone metastatic cancer-secreted extracellular factors are capable of modifying the bone microenvironment through interacting with bone cells, including osteoblasts. Reticulum ribosome-binding protein 1 (RRBP1) is substantially expressed in certain bone metastatic cancer cells. This study was undertaken to determine whether RRBP1 from bone metastatic cancer cells affects the osteoblastic phenotype expression. Breast and prostate cancer cells, MDA-MB-231 and PC3, were cultured, respectively, followed by collecting conditioned mediums (CMs) and identifying the abundance of RRBP1 in CMs using LC-MS/MS. MC3T3-E1 cells were cultured with a mixed medium (including CMs from shRRBP1-transduced two-type cancer cells) with or without endoplasmic reticulum (ER) stress inhibitor 4-PBA, followed by measuring the levels of osteoblastic phenotype expression and biomarkers of ER stress using western blotting, qPCR, and ARS staining, respectively. Similar experiments were performed in shRrbp1-transduced MC3T3-E1 cells cultured with a mixed medium (including CMs from the two-type cancer cells). Bone formation parameters were measured in the tibia of nude mice injected with shRRBP1-transduced two-type cancer cells using micro-CT analysis. These results showed that RRBP1 is the sole shared high-abundance protein in CMs from the two-type cancer cells, involving osteoblast differentiation. CMs from shRRBP1-transduced two-type cells boosted the osteoblastic phenotype expression partially through increasing ER stress. CMs from the two-type cancer cells partially offset the similar alterations induced by shRrbp1 in MC3T3-E1 cells. Injection with shRRBP1-transduced two-type cells ameliorated the bone lesions in nude mice. Therefore, RRBP1 depletion of bone metastatic cancer enhanced the osteoblastic phenotype expression, suggesting a role of RRBP1 in the bone microenvironment.

Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis.

Contacts between organelles create microdomains that play major roles in regulating key intracellular activities and signaling pathways, but whether they also regulate systemic functions remains unknown. Here, we report the ultrastructural organization and dynamics of the inter-organellar contact established by sheets of curved rough endoplasmic reticulum closely wrapped around the mitochondria (wrappER). To elucidate the in vivo function of this contact, mouse liver fractions enriched in wrappER-associated mitochondria are analyzed by transcriptomics, proteomics, and lipidomics. The biochemical signature of the wrappER points to a role in the biogenesis of very-low-density lipoproteins (VLDL). Altering wrappER-mitochondria contacts curtails VLDL secretion and increases hepatic fatty acids, lipid droplets, and neutral lipid content. Conversely, acute liver-specific ablation of Mttp, the most upstream regulator of VLDL biogenesis, recapitulates this hepatic dyslipidemia phenotype and promotes remodeling of the wrappER-mitochondria contact. The discovery that liver wrappER-mitochondria contacts participate in VLDL biology suggests an involvement of inter-organelle contacts in systemic lipid homeostasis.

Ribosome Binding Protein 1 Correlates with Prognosis and Cell Proliferation in Bladder Cancer.

INTRODUCTION: Ribosome binding protein 1 (RRBP1) is reported to be correlated with tumor formation and progression. However, the role of RRBP1 in bladder cancer is unclear. In this study, we aimed to investigate the expression of RRBP1 and its influence on cell proliferation in bladder cancer. METHODS: Quantification real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were used to detect the expression levels of RRBP1 in 138 bladder cancer and matched adjacent normal bladder tissues. Then, the clinical significance of RRBP1 in bladder cancer was evaluated. The effect of RRBP1 on cell proliferation and its potential mechanism were further explored. RESULTS: Results show that the mRNA levels of RRBP1 in bladder cancer were significantly higher compared with those in normal tissues (P< 0.001). IHC results show the high-expression rate of RRBP1 in bladder cancer was 68.8%, which was significantly greater than those in normal tissues (40.6%, P< 0.001). RRBP1 high-expression was significantly associated with differentiation, T stage and lymph node metastasis in bladder cancer (P< 0.05). The overall survival time of patients with RRBP1 high-expression was significantly reduced compared to those with RRBP1 low-expression. Moreover, RRBP1 overexpression significantly promoted cell proliferation, which was correlated with Smad1/Smad3/TGF-ß1 signal pathway. CONCLUSION: RRBP1 high-expression correlates with prognosis and promotes cell proliferation in bladder cancer, which could be a potential biomarker.

High glucose may promote the proliferation and metastasis of hepatocellular carcinoma via E2F1/RRBP1 pathway.

AIMS: Diabetes is considered as one of the important risks in the progression of Hepatocellular carcinoma(HCC). Ribosome binding protein 1 (RRBP1), a rough endoplasmic reticulum protein, plays an essential role in diabetes and various cancer. E2F transcription factor 1 (E2F1), an upstream transcription factor of RRBP1, shows promoting tumor progression effect in multifarious cancers. In this research, we tried to identify whether regulating E2F1/RRBP1 pathway could inhibit the proliferation and metastasis of HepG2 cells induced by high glucose. MAIN METHODS: Proteomic, bioinformatics, molecular biology including RT-qPCR and Western blot, cell biology containing Cell Counting Kit-8 (CCK-8), wound healing assay and transwell assay, and biochemistry analyses incorporating Luciferase assay and CHIP assay were used in this study. KEY FINDINGS: High glucose promoted the proliferation and metastasis of HepG2 cells through up-regulating the expression of RRBP1. Bioinformatics analysis predicted that E2F1 might be the transcription factor of RRBP1. Knocking-down of E2F1 down-regulated mRNA and protein expression levels of RRBP1 in HepG2 cells significantly and suppressed the proliferation, migration and invasion of cells remarkably, Reverse effect was observed in cells that E2F1 was overexpressed. Meanwhile, luciferase and CHIP assay determined that E2F1 could bind to the RRBP1 promoter and promote the transcription of RRBP1. Finally, rescue assay verified the important role of RRBP1/E2F1 axis in the process of HepG2 cells proliferation and metastasis. SIGNIFICANCE: All of the above provided possibility to improve the efficiency of HCC complicated with diabetes treatment by regulating the E2F1/RRBP1 pathway.

Correlation between reticulum ribosome-binding protein 1 (RRBP1) overexpression and prognosis in cervical squamous cell carcinoma.

Our purpose was to evaluate the correlation between endoplasmic reticulum ribosomal binding protein 1 (RRBP1) expression in cervical squamous cell carcinoma (CSCC) and poor patient prognosis. RRBP1 is a nascent transporter that is situated on the rough endoplasmic reticulum (ER). It adjusts to the secretion of proteins in cells and alleviates ER stress, thus stimulating cell proliferation. An immunohistochemical (IHC) study was conducted to detect the expression level of RRBP1 on 96 CSCC tissue samples. Western blot and Quantitative real-time polymerase chain reaction (qRT-PCR) were performed to compare the expression levels of RRBP1 in cervical squamous cell carcinoma with healthy cervical tissues. An overexpression of RRBP1 was observed in CSCC tissues, and the expression level was associated with FIGO stage (Stage I vs. II: 52.6% vs. 74.1%, p = 0.030), and lymph node metastasis (No vs. Yes: 61.5% vs. 92.3%, p = 0.031) but not patient age and tissue differentiation. Univariate survival analysis indicated that prognosis was associated with the expression level of RRBP1 and tissue differentiation and lymph node metastasis. Analysis of the multi-factor survival Cox model proved that RRBP1 was an independent prognostic factor. In conclusion, compared with healthy cervical tissues, RRBP1 was overexpressed in CSCC tissues, illustrating that RRBP1 may be a new biomarker for the diagnosis of CSCC. The study on RRBP1 may contribute to exploring the pathogenesis of CSCC and may also guide targeted therapy for CSCC in the future.

RRBP1 is highly expressed in prostate cancer and correlates with prognosis.

Objective: Recently, ribosome binding protein 1 (RRBP1) is reported to be involved in tumorigenesis. However, the expression and clinical significance of RRBP1 in prostate cancer (PCa) remains unknown. This study is aimed to investigate the expression and clinical significance of RRBP1 in PCa. Materials and methods: RRBP1 expression was firstly detected in 6 cases of PCa and matched adjacent non-cancerous prostate tissues by reverse transcription-quantitative PCR (RT-qPCR) and Western blot. Then, RRBP1 expression was further detected in 127 cases of PCa and 40 cases of non-cancerous prostate tissues by immunohistochemistry (IHC). The relationship of RRBP1 with clinical-pathological characters and patients' prognosis was analyzed in PCa. Results: RT-qPCR and Western blot analysis showed that RRBP1 expression levels in PCa tissues were significantly higher compared with those in matched adjacent non-cancerous prostate tissues. IHC results shown that the high-expression rate of RRBP1 in PCa was 69.3%, which was significantly greater than those in non-cancerous prostate tissues (15.0%, P<0.001). RRBP1 expression was significantly associated with T stage, lymph node metastasis, PSA and Gleason score in PCa. Survival analysis indicated that patients with RRBP1 low-expression presented longer survival time compared with those with RRBP1 high-expression. Moreover, RRBP1 as well as T stage, lymph node metastasis and Gleason score could serve as independent prognostic factors in PCa. Conclusion: RRBP1 is highly expressed in PCa and correlates with prognosis, which may serve as a potential biomarker in PCa.

Expression of RRBP1 in epithelial ovarian cancer and its clinical significance.

Hematopoietic pre-B cell leukemia transcription factor (PBX)-interacting protein (RRBP1) has been shown to participate in various aspects of malignancies. The clinical significance of RRBP1 and its involvement in the epithelial ovarian cancer have yet to be studied. The aim of the present study was to investigate the expression of RRBP1 in epithelial ovarian cancer (EOC) and its relationship with clinical characteristics and prognosis. We evaluated the mRNA and protein expression levels of RRBP1 by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (n=45). Immunohistochemistry and data analysis were used to examine the relationship between the expression level of RRBP1 and the clinicopathological features and prognosis of epithelial ovarian cancer. RRBP1 was highly expressed in EOC (P<0.001). The specimens were obtained from 108 patients undergoing surgery to treat epithelial ovarian cancer. RRBP1 expression was obviously related to Federation International of Gynecologie and Obstetrigue (FIGO) stage (P<0.001), histological grade (P=0.021), histological type (P=0.004), and lymph node metastasis (P=0.012) but was not related to patient age (P=0.385) or preoperative carbohydrate antigen125 (CA125) level (P=0.238). Univariate analysis showed that the prognosis of the epithelial ovarian cancer patients was related to the age of the patients, the FIGO stage, and the expression level of RRBP1 (P<0.05). Patients with higher RRBP1 expression had significantly worse overall survival (OS) (P=0.003) and disease-free survival (DFS) (P<0.001). Multivariate survival analysis proved that RRBP1 was an independent predictor of OS (P=0.003) and DFS (P<0.001). RRBP1 plays an important role in predicting the prognosis of EOC. These results show that RRBP1 is a potential target for the treatment of epithelial ovarian cancer.

RRBP1 overexpression is associated with progression and prognosis in endometrial endometrioid adenocarcinoma.

BACKGROUND: Currently, ribosome-binding protein 1 (RRBP1) is considered to be a novel oncogene that is overexpressed in colorectal cancer, lung cancer, mammary cancer, esophageal cancer and other carcinomas. However, the relationship between RRBP1 and endometrioid-type endometrial carcinoma (EC) remains unknown. Our purpose is to explore the function of RRBP1 in endometrioid-type endometrial carcinoma. METHODS: We investigated the expression of RRBP1 protein by immunohistochemistry on paraffin-embedded surgical specimens from one hundred thirty patients with endometrioid-type endometrial carcinoma. We also evaluated the differences in RRBP1 expression between endometrial cancer samples (n = 35) and normal endometrial tissues (n = 19) by western blotting. RESULTS: RRBP1 was more highly expressed in endometrial cancer samples than in normal samples (P < 0.05). High levels of expression of RRBP1 were strongly correlated with pathological features, such as the Federation of Gynecology and Obstetrics (FIGO) stage, histological grade, depth of myometrial invasion and lymph node metastasis (P < 0.05). Furthermore, RRBP1 expression was an independent prognostic factor for overall survival (OS) and disease-free survival (DFS) in patients with EC (both P < 0.05). CONCLUSION: This experiment identifies the utility of RRBP1 in predicting EC prognosis, revealing that it may be a potential target for therapeutics of EC.

Expression and significance of RRBP1 in esophageal carcinoma.

OBJECTIVE: This study was to investigate the expression and clinical significance of RRBP1 in esophageal carcinoma. MATERIALS AND METHODS: RRBP1 expression was detected in 120 esophageal carcinoma and matched adjacent normal tissues, and the relationship of RRBP1 with clinicopathological characteristics and prognosis was analyzed. RESULTS: RRBP1 was highly expressed in esophageal carcinoma tissues compared with matched adjacent normal tissues (P<0.05). Moreover, RRBP1 expression was associated with T stage, lymph node metastasis, and TNM stage in esophageal carcinoma (P<0.05). Survival analysis revealed that RRBP1, T stage, lymph node metastasis, and TNM stage were significantly associated with patients' prognosis. CONCLUSION: RRBP1 is highly expressed in esophageal carcinoma and can serve as a potential biomarker to predict patients' prognosis.

Expression profile of rrbp1 genes during embryonic development and in adult tissues of Xenopus laevis.

Recent studies suggest that ribosome-binding protein 1 (RRBP1) is involved in multiple diseases such as tumorigenesis and cardiomyopathies. However, its function during embryonic development remains largely unknown. We searched Xenopus laevis database with human RRBP1 protein sequence and identified two cDNA sequences encoding Xenopus orthologs of RRBP1 including rrbp1a (NM_001089623) and rrbp1b (NM_001092468). Both genes were firstly detected at blastula stage 8 with weak signals in animal hemisphere by whole mount in situ hybridization. Evident expression of rrbp1 was mainly detected in cement gland and notochord at neurula and tailbud stages. Heart expression of rrbp1 was detected at stage 36. RT-PCR results indicated that very weak expression of rrbp1a was firstly detected in oocytes, followed by increasing expression until stage 39. Differently, very weak expression of rrbp1b was firstly observed at stage 2, and then maintained at a lower level to stage 17 followed by an intense expression from stages 19-39. Moreover, both expression profiles were also different in adult tissues. This study reports Xenopus rrbp1 expression during early embryonic development and in adult tissues. Our study will facilitate the functional analysis of Rrbp1 family during embryonic development.