[Corrigendum] RON and c­Met facilitate metastasis through the ERK signaling pathway in prostate cancer cells.

Subsequently to the publication of the above article, the authors have discovered that the version of Fig. 5 included in the paper was an incorrect version, and that two pairs of data panels were inadvertently included in Fig. 6D (the data panels for the NC+migration and NC+HGF+U0126+invasion experiments for the PC3 cells, and the data panels for the NC+invasion and NC+HGF+U0126+invasion experiments for the DU145 cells) that contained overlapping data derived from the same source. These data were intended to represent the results obtained under different experimental conditions. Furthermore, the GAPDH control bands in Fig. 4A (DU145 cells) and the p­ERK1/2 bands in Fig. 6A (PC3 cells) were incorrectly chosen for these figures. After having consulted the original data, the authors discovered that unintended errors were made in assembling the data for these graphs. In uploading the corrected version of Fig. 5, Fig. 3C and D and Fig. 4C and D were adjusted accordingly. The corrected versions of Figs. 3, 4, 5, and 6 are shown on the subsequent pages. The authors regret the errors that were made during the preparation of the published figures, and confirm that these errors did not affect the conclusions reported in the study. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish a Corrigendum, and all the authors agree to this Corrigendum. Furthermore, they apologize to the readership for any inconvenience caused. [Oncology Reports 37: 3209­3218, 2017; DOI: 10.3892/or.2017.5585].

The MYH9 Cytoskeletal Protein Is a Novel Corepressor of Androgen Receptors.

In the progression of castration-resistant prostate cancer (CRPC), the androgen receptor (AR) that serves as a transcription factor becomes the most remarkable molecule. The transcriptional activity of AR is regulated by various coregulators. As a result, altered expression levels, an aberrant location or activities of coregulators promote the development of prostate cancer. We describe herein results showing that compared with androgen-dependent prostate cancer (ADPC) cells, AR nuclear translocation capability is enhanced in androgen-independent prostate cancer (AIPC) cells. To gain insight into whether AR coregulators are responsible for AR translocation capability, we performed coimmunoprecipitation (CO-IP) coupled with LC-MS/MS to screen 27 previously reported AR cofactors and 46 candidate AR cofactors. Furthermore, one candidate, myosin heavy chain 9 (MYH9), was identified and verified as a novel AR cofactor. Interestingly, the distribution of MYH9 was in both the cytoplasmic and nuclear compartments yet was enriched in the nucleus when AR was knocked down by AR shRNA, suggesting that the nuclear translocation of MYH9 was negatively regulated by AR. In addition, we found that blebbistatin, an inhibitor of MYH9, not only promoted AR nuclear translocation but also enhanced the expression of the AR target gene PSA, which indicates that MYH9 represses nuclear AR signaling. Taken together, our findings reveal that MYH9 appears to be a novel corepressor of AR plays a pivotal role in the progression of CRPC.

Surface-anchored framework for generating RhD-epitope stealth red blood cells.

Rhesus D (RhD) is one of the most important immunogenic antigens on red blood cells (RBCs). However, the supply of RhD-negative blood frequently faces critical shortages in clinical practice, and the positive-to-negative transition of the RhD antigen remains a great challenge. Here, we developed an alternative approach for sheltering the epitopes on RhD-positive RBCs using a surface-anchored framework, which is flexible but can achieve an optimal shield effect with minimal physicochemical influence on the cell. The chemical framework completely obstructed the RhD antigens on the cell surface, and the assessments of both blood transfusion in a mouse model and immunostimulation with human RhD-positive RBCs in a rabbit model confirmed the RhD-epitope stealth characteristics of the engineered RBCs. This work provides an efficient methodology for improving the cell surface for universal blood transfusion and generally indicates the potential of rationally designed cell surface engineering for transfusion and transplantation medicine.

[Identification of Phenotype and Genotype in One Case with Weak D blood group].

OBJECTIVE: To investigate the phenotype and genotype of the weak D blood group in one case of Chinese Han people. METHODS: Phenotype of blood sample was identified with serologic tests; PCR-SBT was applied for the analysis of genotype and RhD zygosity. RESULTS: Both saline and gel card tests demonstrated this case to be dCcee, which was contrary to glass bead card result. Some of the RBC D epitopes were negative.c.1022T>A allele was identified with PCR-SBT and the zygosity analysis showed this case to be D/d. CONCLUSION: RHD*1022 A is more suitable to be categorized as weak partial D other than weak D in a Chinese Han people.

Toehold integrated molecular beacon system for a versatile non-enzymatic application.

A molecular beacon (MB) is an oligonucleotide hybridization probe with a hairpin-shaped structure that leads to specific and instantaneous nucleic acid hybridization, enabling a variety of applications. However, integration of additional module sequences interferes with the performance of MBs and increases the complexity of sequence design. Herein, we develop and characterize a toehold integrated molecular beacon (ToMB) strategy for nucleic acid hybridization, where the reaction rate can be flexibly regulated by a target-induced MB conformational switch. Using this basic mechanism, the ToMB is capable of identifying nucleic acids with high specificity and a wider linearity range compared with the conventional molecular beacon system. We further applied the ToMB to the construction of a hybridization chain reaction system and a basic OR logic gate VJHto explore its programmability and versatility. Our results strongly suggest that the novel ToMB can act as a powerful nano-module to construct universal and multifunctional biosensors or molecular computations. Graphical abstract Molecular beacon is employed as a flexible and switchable spacer to control the toehold-mediated strand displacement reaction.

[A weak D type 59 case identified in the Chinese Han population].

OBJECTIVE: To study a case with weak D59 phenotype identified among ethnic Han Chinese population. METHODS: Routine serological tests were used to analyze the reaction patterns, and the RhD epitopes were verified with 12 monoclonal antibodies. Sequence-specific primer PCR was applied for typing the weak RhD and RhD zygosity in the proband and his family members. RESULTS: A c.1148T>C variant was identified in the proband, for which serological test indicated a weak D phenotype. RHD zygosity testing confirmed that the proband had a RHD+ /RHD- genotype. CONCLUSION: A weak D59 phenotype was firstly identified in a Chinese individual.

SGK1 inhibition-induced autophagy impairs prostate cancer metastasis by reversing EMT.

BACKGROUND: Despite SGK1 has been identified and characterized as a tumor-promoting gene, the functions and underlying mechanisms of SGK1 involved in metastasis regulation have not yet been investigated in cancer. METHODS: We investigated the cellular responses to GSK650394 treatment and SGK1 silencing (or overexpression) in human prostate cancer (PCa) cell lines and PC3 xenografts by wound healing assay, migration and invasion assay, western blotting, immunofluorescence and immunohistochemistry. RESULTS: In the present study, we found that SGK1 expression positively correlates with human prostate cancer (PCa) progression and metastasis. We show that SGK1 inhibition significantly attenuates EMT and metastasis both in vitro and in vivo, whereas overexpression of SGK1 dramaticlly promoted the invasion and migration of PCa cells. Our further results suggest that SGK1 inhibition induced antimetastatic effects, at least partially via autophagy-mediated repression of EMT through the downregulation of Snail. Moreover, ectopic expression of SGK1 obviously attenuated the GSK650394-induced autophagy and antimetastatic effects. What's more, dual inhibition of mTOR and SGK1 enhances autophagy and leads to synergistic antimetastatic effects on PCa cells. CONCLUSIONS: Taken together, this study unveils a novel mechanism in which SGK1 functions as a tumor metastasis-promoting gene and highlights how co-targeting SGK1 and autophagy restrains cancer progression due to the amplified antimetastatic effects.

SGK1 inhibition induces autophagy-dependent apoptosis via the mTOR-Foxo3a pathway.

BACKGROUND: Although inhibition of SGK1 has been shown to delay cancer progression, the underlying mechanisms have not yet been elucidated. METHODS: We investigated the cellular responses to GSK650394 treatment and SGK1 silencing (or overexpression) in human prostate cancer (PCa) cell lines and PC3 xenografts by flow cytometry, western blotting, immunofluorescence, transmission electron microscopy and immunohistochemistry. RESULTS: In the present study, we demonstrated that SGK1 inhibition, mediated by either GSK650394 or SGK1 shRNA, induced G2/M arrest, apoptosis and autophagy. Furthermore, 3MA-mediated autophagy inhibition attenuated SGK1 inhibition-induced apoptosis, suggesting that induction of autophagy precedes apoptosis. Moreover, ectopic expression of SGK1 significantly attenuated the GSK650394-induced effects. Suppression of mTOR and Foxo3a phosphorylation is critical for blockade of SGK1-induced autophagy and apoptosis, at least partially via pFoxo3a (S253)-LC3 and pFoxo3a (S253)-p27 interactions. Dual inhibition of mTOR and SGK1 enhances autophagy activation and leads to synergistic cytocidal effects in PCa cells. CONCLUSIONS: In summary, our findings show that SGK1 inhibition exhibits significant antitumour effects against PCa in vitro and in vivo. This study uncovered a novel mechanism of SGK1 inhibition in PCa, which is mediated, at least in part, by inducing autophagy-dependent apoptosis via the mTOR-Foxo3a pathway.

Association between human papillomavirus and prostate cancer: A meta-analysis.

Observational studies have suggested an association between human papillomavirus (HPV) infection and the risk of prostate cancer (PCa). However, the association between HPV infection and the risk of PCa remains unclear. The aim of the present meta-analysis study was to investigate whether HPV serves a role in increasing the risk of PCa. Relevant previous studies up to May 2015 were searched in PubMed, Web of Science, Cochrane library, Chinese National Knowledge Infrastructure, China Wan Fang database and China Biomedical Literature Database. A random-effects model or fixed-effects model was employed to determine odds ratios (ORs) with 95% confidence intervals (CIs), when appropriate. Heterogeneity was evaluated using Q and I2 statistical analysis. A total of 24 case-control studies involving 971 patients and 1,085 controls were investigated to estimate the association between HPV infection and PCa risk. The pooled estimate for OR was 2.27 (95% CI, 1.40-3.69). Stratified pooled analyses were subsequently performed according to the HPV detection methods, geographical regions, publication years and types of tissue. Sensitivity analysis based on various exclusion criteria maintained the significance with respect to PCa individually. Little evidence of publication bias was observed. The meta-analysis suggested that HPV infection is associated with increasing risk of PCa, which indicated a potential pathogenetic link between HPV and PCa.

RON and c-Met facilitate metastasis through the ERK signaling pathway in prostate cancer cells.

Prostate cancer (PCa) is a metastatic malignant cancer driven by complex pathological mechanisms and characterized by poor long-term prognosis. Metastasis is the main cause of death of PCa patients, yet the molecular mechanisms of this process are poorly understood. In the present study, positive co-expression of RON and c-Met was observed in human clinical PCa tissues (biopsy material), as detected by immunohistochemical staining and quantitative real-time PCR. We investigated this further in PCa cells, demonstrating that the inhibition of RON and c-Met with foretinib (GSK1363089) suppressed metastasis and promoted the reversal of the epithelial-to-mesenchymal transition (EMT) in PCa cells. Furthermore, the invasion and migration of PCa cells were enhanced by the exogenous activation of RON with MSP and c-Met with HGF, whereas silencing of RON and c-Met attenuated the invasion and metastasis of the PCa cells. Our data also demonstrated that HGF/c-Met, but not the MSP-RON signaling pathway may be the dominant mechanism for PCa EMT. We further revealed that RON and c-Met facilitate metastasis via ERK1/2 signaling. These findings indicate that RON and c-Met facilitate metastasis through ERK1/2 signaling and that targeting RON and c-Met with foretinib may be an attractive therapeutic option for suppressing PCa metastasis.

Colorimetric detection of gene transcript by target-induced three-way junction formation.

Gene transcript often varies by alternative splicing, which plays different biological role that results in diversity of gene expression. Therefore, a simple and accurate identification of targeted transcript variant is of prime importance to achieve a precise molecular diagnosis. In this work, we presented a three-way junction based system where two split G-quadruplex forming sequences were coupled into two probes. Only upon the introduction of target gene transcript that offering a specific recognizable splicing site did the two probes assembled into three way junction conformation in a devised process, thus providing a functional G-quadruplex conformation that greatly enhanced hemin peroxidation. A notable resolution for gene splicing site detection was achieved. The detection limitation by colorimetric assay was 0.063µM, and this system has been proved to discriminate even in a single base false level around splicing site (about 3 times of single mismatched analyte to gain an equal signal by perfect analyte ). Furthermore, recoveries of 78.1%, 88.1%, 104.6% were obtained with 0.75µM, 0.25µM, 0.083µM of target, respectively, showing a capacity to further exploit a simple equipped device for gene transcript detection.

[Study of FN1 and ZNF438 gene expression negatively regulated by androgen receptor in androgen-independent LNCaP cells].

OBJECTIVE: To verify whether FN1 and ZNF438 are the androgen receptor(AR) target genes in LNCaP-AI cells and investigate the effects of AR exerts on FN1 and ZNF438 gene expression. METHODS: ChIP-PCR and agarose gel electrophoresis were performed to verify the fact that AR acted on FN1 and ZNF438 gene. Subsequently, LNCaP-AI cells were treated with dihydrotestosterone(DHT)and lentivirus transfection to down-regulate AR expression. The expression of FN1 and ZNF438 gene in mRNA and protein levels were analyzed by RT-qPCR and Western blot. RESULTS: FN1 and ZNF438 gene enrichment of AR-ChIP group were 7.274±0.290 and 6.843±0.078, significantly higher than the IgG-ChIP group of 1.004±0.113 and 1.000±0.014 (t(FN1)=34.91, t(ZNF438)=128.377, P<0.05). Differences were statistical significance. After DHT stimulation, the expression of FN1 and ZNF438 gene in mRNA and protein levels were 0.434±0.050 and 0.069±0.042, significantly lower than the control group of 1.000±0.016 and 1.025±0.277 (t(FN1)=18.532, t(ZNF438)=5.905, P<0.05). Differences were statistical significance. Moreover, after AR down-regulation, the expression of FN1 and ZNF438 gene in mRNA and protein levels were 17.579±4.415 and 1.895±0.424, significantly higher than the control group of 1.028±0.445 and 1.041±0.190 (t(FN1)=6.461, t(ZNF438)=3.184, P<0.05). Differences were statistical significance. CONCLUSIONS: FN1 and ZNF438 gene are AR negatively regulated target genes in LNCaP-AI cells. The study might provide a new sight to further explore the mechanism of LNCaP-AI cells grow in androgen-depleted conditions.

[Pathogenesis study of inherited dysfibrinogenemia].

OBJECTIVE: To explore the pathogenesis of a family with inherited dysfibrinogenemia. METHODS: Coagulation parameters of peripheral venous blood of a family with inherited dysfibrinogenemia from November 2012 were measured. And platelet and fibrinogen functions were examined by thromboelastogram. The antigen concentration of fibrinogen was detected by immune nephelometry. All exons and exon-intron boundaries of FGA, FGB and FGG were amplified and subjected to mutation screening by direct/reverse sequencing. And the influences of mutant fibrinogen structure and function were analyzed and predicated by a molecular structure model. RESULTS: The values of activated partial thromboplastin time (APTT), D-dimer and fibrinogen antigen of the propositus and his mother (I-2), younger brother (II-3), younger sister (II-2) and daughter (III-1) were all in normal reference value ranges.However thrombin time (TT) was significantly prolonged and the activity of fibrinogen was much lower compared to its antigenicity. Thromboelastogram indicated normal function of platelet and impaired function of fibrinogen of I-2, II-2 and III-1.However the fibrinogen functions of proband and II-3 became much more impaired. Mutation screening demonstrated the homozygous mutation of proband and II-3 while I-2, II-2 and III-1 showed heterozygous mutation of FGG c.1001 A>C (p. Asn308Thr). No mutation was detected among other family members and reducing SDS-PAGE immunoblot showed no variants. Asn308, located at the interface of fibrinogen dimmer, participated in the fibrous structure assembling from the structure model. And mutation at this position will affect the stability of fiber structure. CONCLUSION: FGG c.1001 A>C mutation may account for dominant genetic dysfibrinogenemia in these family members.