Bo Yu

Harbin Medical University, Charbin, Heilongjiang Sheng, China

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Publications (64)129.28 Total impact

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    ABSTRACT: Metastatic melanoma, the primary cause of skin cancer-related death, warrants new diagnostic and therapeutic approaches that target the regulatory machinery at molecular level. The heterogeneity and complexity of melanoma result in the difficulty to find biomarkers and targets for early detection and treatment. Here, we investigated metastasis-associated proteins by comparing the proteomic profiles of primary cutaneous melanomas to their matched lymph node metastases, which minimizes heterogeneity among samples from different patients. Results of two-dimensional gel electrophoresis (2-DE) followed by proteomic analysis revealed eight differentially expressed proteins. Among them, seven proteins (α-enolase, cofilin-1, LDH, m-β-actin, Nm23, GRP78, and MDA-9) showed increased and one (annexin A2) showed decreased expression in metastatic lymph node tissues than in primary melanomas. MDA-9 and GRP78 were the most highly expressed proteins in lymph node metastases, which was validated by immunohistochemical staining. Moreover, exosomes from serum samples of metastatic melanoma patients contained higher levels of MDA-9 and GRP78 than those of patients without metastases, indicating the potential of MDA-9 and GRP78 to be biomarkers for early detection of metastasis. Further, small interfering RNA (siRNA)-mediated knockdown confirmed a functional role for MDA-9 and GRP78 to promote cell invasion in the A375 cells. Finally, we showed that GRP78 co-localized with MDA-9 in 293T cells. Taken together, our findings support MDA-9, co-expressed with GRP78, as a melanoma protein associated with lymph node metastasis. Investigating how MDA-9 and GRP78 interact to contribute to melanoma metastasis and disease progression could reveal new potential avenues of targeted therapy and/or useful biomarkers for diagnosis and prognosis.
    Tumor Biology 12/2014; · 2.52 Impact Factor
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    ABSTRACT: Background In our previous researches, we have found that apoptosis was induced in the medial prefrontal cortex (mPFC) of post-traumatic stress disorder (PTSD) rats. Endoplasmic reticulum (ER) stress-induced apoptosis has been implicated in the development of several disorder diseases. The aim of this study was to investigate whether endoplasmic reticulum-related pathway is involved in single-prolonged stress (SPS) induced apoptosis in the mPFC of PTSD rats by examining the expression levels of ATF6 alpha (ATF6¿), two important downstream molecular chaperones of ATF6¿ in the ER stress: Glucose-regulated protein (GRP) 78 and ERP57, and apoptotic factors caspase 12, caspase 9, and caspase 3.ResultsOur results of Morris Water Maze (MWM) test showed that after SPS exposure, a striking increase of the escape latency was observed in SPS rats at day 1 through day 6, and SPS rats had much less time spent in target quadrant compared to control rats ( P < 0.01). And From immunofluorescence assays, we found that there was a gradual increase on the protein expression of ATF6¿ in response to SPS, which indicated ATF6¿ was activated by SPS. And additionally, immunohistochemistry assays, western blotting and reverse transcription-polymerase chain reaction (RT-PCR) showed that the immunoreactivity, protein and mRNA expression of GRP78 and ERP57 increased on 1, 4 days, and peaked on 7 days after SPS exposure, which revealed that SPS triggered inductions of GRP78 and ERP57 in the mPFC neurons. Moreover, RT-PCR assays demonstrated that there were up-regulations in the transcripts levels of caspase 12, caspase 9, and caspase 3 in response to SPS, which were according with the proteins changes of these apoptotic factors and indicated that ER stress and the activation of caspases contributed to SPS.Conclusion Current data in this study highlight that SPS induced ATF6¿-dependent Endoplasmic reticulum stress and ER-related apoptosis in the mPFC neurons, which indicated that the endoplasmic reticulum pathway may be involved in PTSD-induced apoptosis.
    BMC Neuroscience 10/2014; 15(1):115. · 3.00 Impact Factor
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    ABSTRACT: We aimed to investigate the blood brain barrier (BBB) change caused by subarachnoid hemorrhage (SAH) and to explore the molecular mechanisms of acute brain injury after SAH. The SD rat model of SAH was firstly established by endovascular filament perforation technique. The changes of regional cerebral blood flow (rCBF), BBB permeability and ultrastructure of brain tissue at different time points after SAH were respectively observed by Doppler flowmetry, evans blue extravasation and transmission electron microscopy. Meanwhile, the expression changes of Claudin-5, Occludin, Zo-1 and Caveolin-1 were detected by immunohistochemistry and Western blot. Furthermore, the expressions of Akt, P-Akt and Foxo1A were also measured by Western blot. The change of BBB permeability showed two peaks at 3 and 72 h after SAH, corresponding to the change of rCBF. The BBB tight junction opening can be observed after SAH, and the largest opening was occurred at 3 h and 72 h. There was no significant change in Caveolin-1, Claudin-5 and Akt expressions after SAH (P > 0.05), while Zo-1 and Occludin were significantly down-regulated (P < 0.05). The expression of P-Akt was obviously reduced at 30 min and then increased at 1 and 24 h, while Foxo1A was up-regulated at 1 and 24 h after SAH (P < 0.05). Down-regulated Zo-1 and Occludin, as well as Akt/FOXO signaling pathway may be involved in the regulation of tight junction opening and the BBB permeability in the early stage after SAH.
    Metabolic Brain Disease 10/2014; · 2.33 Impact Factor
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    ABSTRACT: Abstract Background: The HLA-B*58:01 allele is associated with allopurinol-induced severe cutaneous adverse drug reactions (sCADR) in certain geographic regions, but the diversity of the correlation is large. In addition, the currently available HLA-B*58:01 testing methods are too laborious for use in routine clinical detection. The objective of this study was to develop a new, convenient method for the detection of HLA-B*58:01 and to investigate the association of HLA-B*58:01 with allopurinol-induced sCADR in a Han Chinese population. Methods: A new method combining sequence-specific primers (SSP) and TaqMan probe amplification was developed in this study and was used to detect the HLA-B*58:01 in 48 allopurinol-induced sCADR, 133 allopurinol-tolerant, and 280 healthy individuals. The accuracy, sensitivity, and specificity were assessed by a commercial PCR-SSP HLA-B typing kit. The low limit of detection was detected by serial dilution of an HLA-B*58:01-positive DNA template. Results: The new method successfully identified HLA-B*58:01 in thousands of HLA-B alleles, and the results for 344 DNA samples were perfectly concordant with the results of the commercial PCR-SSP HLA-B kit. The analytical sensitivity is 100% and the specificity is over 99%. The low limit of detection of this assay is 100 pg DNA, which was 10 times more sensitive than the commercial PCR-SSP kit. HLA-B*58:01 was present in 93.8% of the patients with sCADR, 7.5% of the allopurinol-tolerant patients, and 12.1% of the healthy controls. The frequency of HLA-B*58:01 was significantly higher in the sCADR group than in the control group (p<0.0001). However, there was no significant difference between the allopurinol-tolerant and control groups (p=0.1547). Conclusions: HLA-B*58:01 has a strong association with allopurinol-induced sCADR in Han Chinese. The newly developed method is reliable for HLA-B*58:01 detection prior to allopurinol therapy.
    Clinical chemistry and laboratory medicine : CCLM / FESCC. 09/2014;
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    ABSTRACT: Owing to the mounting evidence of serum lipid changes in atherosclerosis, there has been increasing interest in developing new methods for analyzing atherogenic lipoprotein profiles. The separation of lipoprotein and lipoprotein subclasses has been demonstrated using a microchip capillary electrophoresis (CE) system [1]. In contrast to this previous study, the present report demonstrates that sdLDL peak efficiencies can be improved dramatically by adding gold nanoparticles (AuNPs) to the sample. Moreover, NBD C6-ceramide was identified as a satisfactory dye for specific labeling and quantitation of individual serum lipoproteins. The accuracy of the method was evaluated by comparison with ultracentrifuge separated small, dense low-density lipoprotein (sdLDL). A high correlation was observed between these two methods for sdLDL-cholesterol. Lipid levels were investigated between atherosclerotic patients and healthy controls. The variation of serum atherogenic lipoprotein profiles for atherosclerotic patients pre- and post-treatment was assessed by microchip CE. This method has the potential for the rapid and sensitive detection of different lipoprotein classes as well as their subclasses and is therefore suitable for routine clinical applications. Microchip-based atherogenic lipoprotein profile assays will greatly improve the analysis of risk factors in atherosclerosis and will provide useful information for monitoring the effect of therapies on atherosclerotic disease.
    Analytical Biochemistry 09/2014; · 2.58 Impact Factor
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    ABSTRACT: Accumulating evidence suggests that hypoxia-inducible factor 1α (HIF-1α) regulates numerous miRNAs and is crucial for cellular response to hypoxia. However, the relationship between HIF-1α and miR-21 in hypoxic cardiomyocytes is little known. We found that hypoxia induced HIF-1α and miR-21 expression. HIF-1α knockdown increased cell apoptosis and reduced miR-21 expression. Furthermore, we found that HIF-1α transcriptionally enhanced miR-21 promoter activity by binding to its promoter, which required the recruitment of CBP/p300. In addition, we found that miR-21 inhibition increased cell apoptosis and reduced HIF-1α expression, and modulated the PTEN/Akt pathway. Our results indicate that HIF-1α-miR-21 feedback contributes to the adaptation of cardiomyocytes to hypoxia, and has potential as therapeutic target for myocardial ischemia.
    FEBS letters. 06/2014;
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    ABSTRACT: Chimaphilin, 2,7-dimethyl-1,4-naphthoquinone, is extracted from pyrola [Passiflora incarnata Fisch.]. In this study, the anticancer activity and underlying mechanisms of chimaphilin towards human breast cancer MCF-7 cells are firstly investigated. Chimaphilin could inhibit the viability of MCF-7 cells in a concentration-dependent manner, and the IC50 value was 43.30 μM for 24 h. Chimaphilin markedly induced apoptosis through the investigation of characteristic apoptotic morphological changes, nuclear DNA fragmentation, annexin V-FITC/propidium iodide (PI) double staining. Flow cytometry assay revealed that chimaphilin triggered a significant generation of ROS and disruption of mitochondrial membrane potential. Additionally, western blotting assay showed that chimaphilin suppressed Bcl-2 level and enhanced Bad level, then activated caspase-9 and caspase-3, and further activated the poly ADP-ribose polymerase (PARP), finally induced cell apoptosis involving the mitochondrial pathway. Furthermore, free radical scavengers N-acetyl-L-cysteine (NAC) pretreatment test testified that chimaphilin could increase the generation of ROS, then induce cell apoptosis. In general, the present results demonstrated that chimaphilin induced apoptosis in human breast cancer MCF-7 cells via a ROS-mediated mitochondrial pathway.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2014; · 2.99 Impact Factor
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    ABSTRACT: Long noncoding RNAs (lncRNAs) play important regulatory roles in cellular physiology. The contributions of lncRNAs to ischemic heart disease remain largely unknown. The aim of this study was to investigate the profile of myocardial lncRNAs and their potential roles at early stage of reperfusion. lncRNAs and mRNAs were profiled by microarray and the expression of some highly-dysregulated lncRNAs was further validated using polymerase chain reaction. Our results revealed that 64 lncRNAs were up-regulated and 87 down-regulated, while 50 mRNAs were up-regulated and 60 down-regulated in infarct region at all reperfusion sampled. Gene ontology analysis indicated that dysregulated transcripts were associated with immune response, spermine catabolic process, taxis, chemotaxis, polyamine catabolic process, spermine metabolic process, chemokine activity and chemokine receptor binding. Target gene-related pathway analysis showed significant changes in cytokine-cytokine receptor interaction, the chemokine signaling pathway and nucleotide oligomerization domain (NOD)-like receptor signaling pathway which have a close relationship with myocardial ischemia/reperfusion injury (MI/RI). Besides, a gene co-expression network was constructed to identify correlated targets of 10 highly-dysregulated lncRNAs. These lncRNAs may play their roles by this network in post-ischemic heart. Such results provide a foundation for understanding the roles and mechanisms of myocardial lncRNAs at early stage of reperfusion.
    Gene 04/2014; · 2.20 Impact Factor
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    ABSTRACT: Ginsenoside Rb3 is extracted from the plant Panax ginseng and plays important roles in cardiovascular diseases, including myocardial ischemia-reperfusion (I/R) injury. NF-κB is an important transcription factor involved in I/R injury. However, the underlying mechanism of ginsenoside Rb3 in myocardial I/R injury remains poorly understood. In the current study, a model of myocardial I/R injury was induced via oxygen and glucose deprivation (OGD) followed by reperfusion (OGD-Rep) in mouse cardiac myoblast H9c2 cells. Our data demonstrate that ginsenoside Rb3 suppresses OGD-Rep-induced cell apoptosis by the suppression of ROS generation. By detecting the NF-κB signaling pathway, we discover that the protective effect of ginsenoside Rb3 on the OGD-Rep injury is closely related to the inhibition of NF-κB activity. Ginsenoside Rb3 inhibits the upregulation of phospho-IκB-α and nuclear translocation of NF-κB subunit p65 which are induced by ORD-Rep injury. In addition, the extract also inhibits the OGD-Rep-induced increase in the expression of inflammation-related factors, such as IL-6, TNF-α, monocyte chemotactic protein-1 (MCP-1), MMP-2 and MMP-9. However, LPS treatment alleviates the protective roles of ginsenoside Rb3 and activates the NF-κB pathway. Finally, the upstream factors of NF-κB were analyzed, including the Akt/Foxo3a and MAPK signaling pathways. We find that ginsenoside Rb3 pretreatment only decreases the phosphorylation of JNK induced by OGD-Rep injury, an indicator of the MAPK pathway. Importantly, an inhibitor of phospho-JNK, SP600125, protects against OGD-Rep induced apoptosis and inhibited NF-κB signaling pathway, similar to the roles of ginsenoside Rb3. Taken together, our results demonstrate that the protective effect of ginsenoside Rb3 on the OGD-Rep injury is attributed to the inhibition of JNK-mediated NF-κB activation, suggesting that ginsenoside Rb3 has the potential to serve as a novel therapeutic agent for myocardial I/R injury.
    PLoS ONE 01/2014; 9(8):e103628. · 3.53 Impact Factor
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    ABSTRACT: Previously, we found that the naturally occurring stilbene compound resveratrol (RES) could potentiate cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activity. Because some wild-type CFTR activators also potentiate its mutant forms, we investigated effect of RES on the two most common forms of CF-related mutation (deltaF508 and G551D-CFTR). Cell-based fluorescence studies indicated that RES dose-dependently potentiated both deltaF508 and G551D mutant CFTR Cl- channel activities. Transepithelial Cl- currents were stimulated by RES in deltaF508 and G551D mutant CFTR-expressing FRT cells. Further excised inside-out patch-clamp measurements revealed that RES significantly induced the chloride current of deltaF508 and G551D mutant CFTRs by increasing the open time of the channels. In ex vivo studies, RES stimulated fluid secretion in mouse trachea by optical measurement of single gland secretion. These data suggested that RES is a potent deltaF508 and G551D mutant CFTR potentiator, and RES may present a novel class of therapeutic lead compounds in treating cystic fibrosis.
    Pharmazie 11/2013; 68(11):877-81. · 0.96 Impact Factor
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    ABSTRACT: Isoalantolactone, a sesquiterpene lactone, possesses anti-fungal as well as cytotoxic properties. In this study, the effects of Isoalantolactone on cell viability, cell cycle, and apoptosis were investigated in human gastric adenocarcinoma SGC-7901 cells. The results demonstrated that Isoalantolactone induced morphological changes and decreased cell viability. Subsequently, we found that Isoalantolactone induced G2/M and S phase arrest, which was associated with a decrease in the expression level of cyclin B1. Apoptosis triggered by Isoalantolactone was visualized using propidium iodide (PI) and Annexin V-FITC/PI staining. Isoalantolactone-induced apoptosis of SGC-7901 cells was associated with the dissipation of mitochondrial membrane potential (ΔΨ m) that was due to the down-regulation of Bcl-2 and up-regulation of Bax that led to the cleavage of caspase-3. Additionally, it was found that Isoalantolactone was involved in the inhibition of phosphorylation of PI3K/Akt. Isoalantolactone-induced cytotoxicity and apoptosis of SGC-7901 cells involve mitochondria-caspase and PI3K/Akt dependent pathways, which gives the rationale for in vivo studies on the utilization of Isoalantolactone as a potential cancer therapeutic compound.
    Archives of Pharmacal Research 07/2013; · 1.54 Impact Factor
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    ABSTRACT: It has been supposed that green tea polyphenols (GTPs) have neuroprotective effects on brain damage after brain ischemia in animal experiments. Little is known regarding GTPs' protective effects against the blood-brain barrier (BBB) disruption after ischemic stroke. We investigated the effects of GTPs on the expression of claudin-5, occludin, and ZO-1, and the corresponding cellular mechanisms involved in the early stage of cerebral ischemia. Male Wistar rats were subjected to a middle cerebral artery occlusion (MCAO) for 0, 30, 60, and 120 min. GTPs (400 mg/kg/day) or vehicle was administered by intragastric gavage twice a day for 30 days prior to MCAO. At different time points, the expression of claudin-5, occludin, ZO-1, and PKCalpha signaling pathway in microvessel fragments of cerebral ischemic tissue were evaluated. GTPs reduced BBB permeability at 60 min and 120 min after ischemia as compared with the vehicle group. Transmission electron microscopy also revealed that GTPs could reverse the opening of tight junction (TJ) barrier at 60 min and 120 min after MACO. The decreased mRNA and protein expression levels of claudin-5, occludin, and ZO-1 in microvessel fragments of cerebral ischemic tissue were significantly prevented by treatment with GTPs at the same time points after ischemia in rats. Furthermore, GTPs could attenuate the increase in the expression levels of PKCalpha mRNA and protein caused by cerebral ischemia. These results demonstrate that GTPs may act as a potential neuroprotective agent against BBB damage at the early stage of focal cerebral ischemia through the regulation of TJ and PKCalpha signaling.
    BMC Complementary and Alternative Medicine 07/2013; 13(1):187. · 2.08 Impact Factor
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    ABSTRACT: HSV-1-based vectors have been widely used to achieve targeted delivery of genes into the nervous system. In the current study, we aim to use shRNA-containing HSV-1-based gene delivery system for the therapy of HSV-2 infection. Guinea pigs were infected intravaginally with HSV-2 and scored daily for 100 days for the severity of vaginal disease. HSV-2 shRNA-containing HSV-1 was applied intravaginally daily between 8 to 14 days after HSV-2 challenge. Delivery of HSV-2 shRNA-containing HSV-1 had no effect on the onset of disease and acute virus shedding in animals, but resulted in a significant reduction in both the cumulative recurrent lesion days and the number of days with recurrent disease. Around half of the animals in the HSV-2 shRNA group did not develop recurrent disease 100 days post HSV-2 infection. In conclusion, HSV-2 shRNA-containing HSV-1 particles are effective in reducing the recurrence of genital herpes caused by HSV-2.
    Journal of virological methods 07/2013; · 2.13 Impact Factor
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    ABSTRACT: Reestablishment of functional networks after traumatic brain injury (TBI) has been proffered as one of the goals of neural stem cell (NSC) transplantation therapeutics. Gap junctions provide essential means for direct cellular communication by transferring small molecules and ions, which may provide insights into the interplay between grafted NSCs and host cells. Thirty-six adult male Wister rats were used in this study. The controlled cortical impact (CCI) model of brain injury has been performed. Seventy-two hours after CCI injury, animals were randomly assigned to two groups: PBS- and NSC- transplanted group. NSCs-transplanted group received delivery of the NSCs suspension to the cortex below the injury cavity in the ipsilateral hemisphere. At 1, 2, and 4 weeks post-transplantation, we investigated the expression patterns of gap junction-associated connexin 43 (Cx43) in the transplant site and the border of CCI by immunohistochemistry, Western blot and RT-PCR. Our findings showed that Cx43 staining was significantly greater in the transplant site and the border of CCI in the NSCs-transplanted rats compared to the control rats at different time points (p < 0.01 at 1 week, p < 0.05 at 2 and 4 weeks). Significantly higher gene and protein expression of Cx43 was found in NSCs-transplanted rats compared to the control rats in the period of 4 weeks post-transplantation (p < 0.01), and remained at a higher level until 2 weeks with or without NSC transplantation. It is proposed that gap junction-associated Cx43 might participate in NSCs' beneficial effects via gap-junctional coupling by which grafted NSCs integrate into host neural tissue following transplantation after TBI.
    Archives of Medical Science 02/2013; 9(1):132-8. · 1.89 Impact Factor
  • International journal of cardiology 02/2013; · 6.18 Impact Factor
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    ABSTRACT: New strategies for the treatment of advanced melanoma are urgently required. The RAS/RAF/MAPK pathway and c-Src are deregulated in the majority of malignant melanomas, suggesting that they may interact functionally and are involved in the development and progression of the malignancy. Preclinical studies have demonstrated variable inhibition of melanoma cell growth by dasatinib in vitro. Src may act through different downstream signaling pathways. In the present study, we demonstrate that dasatinib induces changes in cell morphology, characterized by an arborized and contracted appearance, and accompanied by a reduction in cell proliferation in primary melanoma cells. This morphological change is demonstrated to be associated with the inhibition of nuclear translocation of activated ERK1/2. Together, these results indicate that Src may promote cell proliferation through the activation of the ERK signaling pathway in melanoma oncogenesis.
    Oncology letters 02/2013; 5(2):527-532. · 0.24 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate neointimal coverage obtained using a new method of polytetrafluoroethylene-covered stent (PCS) implantation combined with underlying longer sirolimus-eluting stent (SES) implantation using optical coherence tomography. Nine patients were enrolled in this study, including patients with coronary artery perforations, original coronary aneurysms, and acquired coronary aneurysms after drug-eluting stent implantation. All patients were first treated with long SES implantation and then with focal PCS implantation. Postprocedural and follow-up angiographic and optical coherence tomographic examinations were performed in all patients, and intravascular ultrasound was performed in 5 patients. All patients were asymptomatic during follow-up, without recurrent angina. There was no stent-edge or stent-segment binary restenosis. Values of late loss for proximal SES segments, PCS segments, and distal SES segments were similar (0.09, 0.07, and 0.04 mm, respectively, p = 0.8113). The mean neointimal thickness of PCS was less than that of proximal and distal SES. However, no malapposed cross sections or uncovered cross sections were found in PCS segments compared with SES segments (p = 0.0011). In conclusion, the combination of PCS and underlying longer SES implantation can offer better angiographic follow-up results. High-resolution optical coherence tomography provided convincing proof of full neointimal coverage of PCS. This new method of combined PCS and SES implantation may be a better choice compared with direct PCS implantation in certain clinical settings.
    The American journal of cardiology 01/2013; · 3.58 Impact Factor
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    ABSTRACT: Mesenchymal stem cells (MSCs) can suppress dendritic cells (DCs) maturation and function, mediated by soluble factors, such as indoleamine 2,3-dioxygenase (IDO), prostaglandin E(2) (PGE(2)), and nitric oxide (NO). Interleukin-10 (IL-10) is a common immunosuppressive cytokine, and the downstream signaling of the JAK-STAT pathway has been shown to be involved with DCs differentiation and maturation in the context of cancer. Whether IL-10 and/or the JAK-STAT pathway play a role in the inhibitory effect of MSCs on DCs maturation remains controversial. In our study, we cultured MSCs and DCs derived from rat bone marrow under different culturing conditions. Using Transwell plates, we detected by ELISA that the level of IL-10 significantly increased in the supernatants of MSC-DC co-cultures at 48 hours. The cell immunofluorescence assay suggested that the MSCs secreted more IL-10 than the DCs in the co-cultures. Adding exogenous IL-10 to the DCs monoculture or MSC-DC co-cultures stimulated IL-10 and led to a decrease in IL-12, and lower expression of the DCs surface markers CD80, CD86, OX62, MHC-II and CD11b/c. Supplementing the culture with an IL-10 neutralizing antibody (IL-10NA) showed precisely the opposite effect of adding IL-10. Moreover, we demonstrated that the JAK-STAT signaling pathway is involved in inhibiting DCs maturation. Both JAK1 and STAT3 expression and IL-10 secretion decreased markedly after adding a JAK inhibitor (AG490) to the co-culture plate. We propose that there is an IL-10 positive feedback loop, which may explain our observations of elevated IL-10 and enhanced JAK1 and STAT3 expression. Overall, we demonstrated that MSCs inhibit the maturation of DCs through the stimulation of IL-10 secretion, and by activating the JAK1 and STAT3 signaling pathway.
    PLoS ONE 01/2013; 8(1):e55487. · 3.53 Impact Factor
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    ABSTRACT: Because of their regenerative and paracrine abilities, cardiac stem cells (CSCs) are the most appropriate, optimal and promising candidates for the development of cardiac regenerative medicine strategies. However, native and exogenous CSCs in ischemic hearts are exposed to various pro-apoptotic or cytotoxic factors preventing their regenerative and paracrine abilities. We examined the effects of H2O2 on mouse CSCs (mCSCs), and observed that hydrogen peroxide (H2O2) treatment induces mCSCs apoptosis via the caspase 3 pathway, in a dose-dependent manner. We then examined the effects of Wnt1 over-expression on H2O2-induced apoptosis in mCSCs and observed that Wnt1 significantly decreased H2O2-induced apoptosis in mCSCs. On the other hand, inhibition of the canonical Wnt pathway by the secreted frizzled related protein 2 (SFRP2) or knockdown of β-catenin in mCSCs reduced cells resistance to H2O2-induced apoptosis, suggesting that Wnt1 predominantly prevents H2O2-induced apoptosis through the canonical Wnt pathway. Our results provide the first evidences that Wnt1 plays an important role in CSCs' defenses against H2O2-induced apoptosis through the canonical Wnt1/GSK3β/β-catenin signaling pathway.
    PLoS ONE 01/2013; 8(3):e58883. · 3.53 Impact Factor
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    ABSTRACT: Metastatic melanoma, the primary cause of skin cancer-related death, warrants new therapeutic approaches that target the regulatory machinery at molecular level. While long noncoding RNAs (lncRNAs) are dysregulated in a number of cancer types, limited data are available on the expression and function of lncRNAs in melanoma metastasis. The primary objective of this study was to investigate the role of 6 metastasis-related lncRNAs in pairs of primary melanoma and matched lymph node metastatic tissues. Among the tested lncRNAs, HOTAIR was the most highly expressed in lymph node metastasis. The role of HOTAIR in melanoma cell motility and invasion was further evaluated by knocking down HOTAIR with siRNAs. Knockdown of HOTAIR resulted in the reduction of motility and invasion of human melanoma cell line A375, as assessed by wound healing assay and Matrigel-based invasion assay. siHOTAIR also suppressed the degradation of gelatin matrix, suggesting that HOTAIR promotes gelatinase activity. Together, our study shows that HOTAIR is overexpressed in metastatic tissue, which is associated with the ability of HOTAIR to promote melanoma cell motility and invasion. These data indicate that lncRNAs may be involved in the metastasis of melanoma and provide support for further evaluation of lncRNAs in melanoma.
    BioMed research international. 01/2013; 2013:251098.

Publication Stats

266 Citations
129.28 Total Impact Points

Institutions

  • 2008–2014
    • Harbin Medical University
      • • Department of Pharmacology
      • • Department of Cardiology
      Charbin, Heilongjiang Sheng, China
  • 2013
    • Massachusetts General Hospital
      • Division of Cardiology
      Boston, MA, United States
    • Anhui Medical University
      Luchow, Anhui Sheng, China
  • 2011–2013
    • Liaoning Normal University
      • School of Life Science
      Lü-ta-shih, Liaoning, China
  • 2009–2013
    • Texas Biomedical Research Institute
      San Antonio, Texas, United States
  • 2012
    • Northeast Normal University
      • Membrane Channel Research Laboratory
      Hsin-ching, Jilin Sheng, China
  • 2010–2011
    • Peking University People's Hospital
      Peping, Beijing, China
    • Fudan University
      Shanghai, Shanghai Shi, China
    • Peking University Third Hospital
      Peping, Beijing, China
    • University of Jinan (Jinan, China)
      Chi-nan-shih, Shandong Sheng, China
  • 2009–2011
    • Peking University
      • Department of Chemical Biology
      Beijing, Beijing Shi, China