Key Laboratory of Cell Biology

Shenyang, China

Key Laboratory of Cell Biology

Shenyang, China
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Liu X.,Liaoning Medical University | You L.,Key Laboratory of Cell Biology | You L.,Shenyang University | Zhou R.,Key Laboratory of Cell Biology | And 3 more authors.
Oncotarget | Year: 2017

Molecular epidemiological studies suggest that microRNA polymorphisms may be associated with an increased risk of coronary heart disease (CHD). However, the results of these studies were inconsistent and inconclusive. To derive a more precise evaluation, we performed a meta-analysis focused on the associations between microRNA polymorphisms and CHD risk. PubMed, Embase, CNKI and Wanfang databases were searched. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to assess the association between microRNA-146a rs2910164, microRNA-196a2 rs11614913, microRNA-499 rs3746444 and microRNA-149 rs71428439 polymorphisms and CHD susceptibility. Heterogeneity, publication bias and sensitivity analysis were conducted to measure the robustness of our findings. A total of thirteen related studies involving 8,120 patients and 8,364 controls were analyzed. Significant associations between microRNA-146a rs2910164 polymorphism and CHD risk were observed in the total population, as well as in subgroup analysis. For microRNA-196a2 rs11614913 and microRNA-499 rs3746444, similarly increased risks were also found. In addition, no significant association was detected between microRNA-149 rs71428439 polymorphism and CHD risk. In conclusion, our metaanalyses suggest that microRNA polymorphisms may be associated with increased risk of CHD development.

Li X.,Key Laboratory of Cell Biology | Li X.,Liaoning Medical University | Li J.,Key Laboratory of Cell Biology | Li J.,Liaoning Medical University | And 2 more authors.
Oncology Reports | Year: 2017

P21 activated kinase 4 (PAK4), as an effector of Cdc42, playing important roles in regulating the processes of cytoskeleton organization. PAK4 has been considered to be an oncogenic protein, which has strong relationship with gastric cancer metastasis. However, the mechanism of PAK4 in regulating gastric cancer metastasis is still not fully understood. In this study, using yeast two-hybrid system, we identified that the eukaryotic elongation factor 1 α l (eEF1A1) is a new binding partner of PAK4. The interaction between PAK4 and eEF1A1 was confirmed by GST pull-down and co-immunoprecipitation. PAK4 co-localized with eEF1A1 in the cytoplasm of gastric cancer cells. Overexpres sion of PAK4 enhanced the expression level of eEF1A1 and vice versa. PAK4 and eEF1A1 could cooperate to promote gastric cancer cell migration and invasion. Furthermore, the expression of PAK4 and eEF1A1 in clinical gastric cancer samples were examined by western blotting and immunohistochemistry. Statistical analysis indicated that there was positive correlation between the expression of PAK4 and eEF1A1. This study demonstrated for the first time that PAK4 interacted with eEF1A1 to promote migration and invasion of gastric cancer cells, thereby providing new insights into the function of PAK4 and eEF1A1 in the progression of gastric cancer.

Shen T.,China Medical University at Heping | Li Y.,Key Laboratory of Cell Biology | Li Y.,Shenyang University | Yang L.,China Medical University at Heping | And 6 more authors.
International Journal of Biochemistry and Cell Biology | Year: 2012

Polo-like kinase 2 (Plk2) is a member of the serine/threonine protein kinase family involved in cell-cycle regulation and cellular response to stresses. It is of great interest to investigate the molecular mechanisms that control the expression of Plk2. Here, using real-time PCR and Western blot assays, we show that trichostatin A (TSA), a histone deacetylase inhibitor, upregulated Plk2 mRNA and protein expression in the human osteosarcoma MG-63 cell line. Luciferase activity analysis of the truncated Plk2 promoter indicated that the region from -1220 to -830 of the Plk2 promoter was sensitive to TSA. Moreover, using the electrophoresis mobility shift assay and chromatin immunoprecipitation assay, we identified two GATA-1 responsive elements at positions -1051 and -949, to which GATA-1 binding was enhanced by TSA under in vitro and in vivo conditions. Immunoprecipitation and Western blot showed that the levels of acetylated GATA-1 were increased with TSA in MG-63 cells, consistent with their binding affinities to the GATA-1 responsive elements. In summary, these data demonstrate that acetylation plays a crucial role in Plk2 expression and acetylation of GATA-1 by TSA treatment may upregulate their DNA-binding affinities, resulting in the activation of Plk2 promoter. These results may contribute to the understanding of the molecular mechanism of Plk2 regulation. © 2011 Elsevier Ltd. All rights reserved.

Guo Q.,Key Laboratory of Cell Biology | Su N.,Key Laboratory of Cell Biology | Zhang J.,Key Laboratory of Cell Biology | Li X.,Key Laboratory of Cell Biology | And 6 more authors.
Oncogene | Year: 2014

Superior cervical ganglia 10 (SCG10), as a microtubule (MT) destabilizer, maintains MT homeostasis and has a critical role in neuronal development, but its function in tumorigenesis has not been characterized. In the present study, we demonstrated that p21-activated kinase 4 (PAK4)-mediated SCG10 phosphorylation regulates MT homeostasis in metastatic gastric cancer. Our results indicate that SCG10 is a physiological substrate of PAK4, which is phosphorylated on serine 50 (Ser50) in a PAK4-dependent manner. Phosphorylated SCG10 regulated MT dynamics to promote gastric cancer cell migration and invasion in vitro and metastasis in a xenograft mouse models. Inhibiting PAK4, either by LCH-7749944 or RNA interference, resulted in the inhibition of Ser50 phosphorylation and a blockade to cell invasion, suggesting that PAK4-SCG10 signaling occurs in gastric cancer cell invasion. Moreover, we demonstrated a strong positive correlation between PAK4 and phospho-Ser50 SCG10 expression in gastric cancer samples. We also showed that high expression of SCG10 phospho-Ser50 is highly correlated to an aggressive phenotype of clinical gastric cancer. These findings revealed a novel function of SCG10 in promoting invasive potential of gastric cancer cells, suggesting that blocking PAK4-mediated SCG10 phosphorylation might be a potential therapeutic strategy for metastasis of gastric cancer. © 2014 Macmillan Publishers Limited.

Wang X.-X.,Shenyang University | Sun B.-F.,CAS Beijing Institute of Genomics | Jiao J.,Shenyang University | Chong Z.-C.,CAS Beijing Institute of Genomics | And 6 more authors.
Oncotarget | Year: 2015

Discovery of 5-hydroxymethylcytosine (5hmC) in mammalian genomes has excited the field of epigenetics, but information on the genome-wide distribution of 5hmC is limited. Globozoospermia is a rare but severe cause of male infertility. To date, the epigenetic mechanism, especially 5hmC profiles involved in globozoospermia progression, remains largely unknown. Here, utilizing the chemical labeling and biotin-enrichment approach followed by Illumina HiSeq sequencing, we showed that (i) 6664, 9029 and 6318 genes contain 5hmC in normal, abnormal, and globozoospermia sperm, respectively; (ii) some 5hmC-containing genes significantly involves in spermatogenesis, sperm motility and morphology, and gamete generation; (iii) 5hmC is exclusively localized in sperm intron; (iv) approximately 40% imprinted genes have 5hmC modification in sperm genomes, but globozoospermia sperm exhibiting a large portion of imprinted genes lose the 5hmC modification; (v) six imprinted genes showed different 5hmC patterns in abnormal sperm (GDAP1L1, GNAS, KCNK9, LIN28B, RB1, RTL1), and five imprinted genes showed different 5hmC patterns in globozoospermia sperm (KCNK9, LIN28B, RB1, SLC22A18, ZDBF2). These results suggested that differences in genome-wide 5hmC patterns may in part be responsible for the sperm phenotype. All of this may improve our understanding of the basic molecular mechanism underlying sperm biology and the etiology of male infertility.

Liu Y.-J.,Key Laboratory of Cell Biology | Guo D.-W.,Key Laboratory of Cell Biology | Tian L.,Key Laboratory of Cell Biology | Shang D.-S.,Key Laboratory of Cell Biology | And 5 more authors.
Neurobiology of Aging | Year: 2010

The mechanism of circulating T cells entry into the brain in Alzheimer's diseases (AD) remains unclear. Here, we showed that peripheral T cells derived from AD patients overexpress CXCR2 to enhance its transendothelial migration. T cells migration through in vitro blood-brain barrier model was effectively blocked by anti-CXCR2 antibody or IL-8 (a CXCR2 ligand) RNAi in human brain microvascular endothelial cells (HBMECs). Amyloid beta (Aβ) injection in rat hippocampus upregulated CXCR2 expression accompanied with increased T cells occurrence in the brain, and this enhanced T cells entry was effectively blocked by CXCR2 antagonist. Furthermore, anti-TNF-α antibody blocked IL-8 production in HBMECs and T cells transendothelial migration caused by the culture supernatant of microglia treated with Aβ. Blockage of intracerebral TNF-α abolished the upregulation of CXCR2 in peripheral T cells and the increased T cells occurrence in the brain induced by Aβ injection in rat hippocampus. These data suggest that CXCR2 overexpression in peripheral T cells is intracerebral microglial TNF-α-dependent and TNF-α primes T cells transendothelial migration in Alzheimer's diseases. © 2008 Elsevier Inc. All rights reserved.

Li X.,Key Laboratory of Cell Biology | Ke Q.,Key Laboratory of Cell Biology | Li Y.,Key Laboratory of Cell Biology | Liu F.,Key Laboratory of Cell Biology | And 2 more authors.
International Journal of Biochemistry and Cell Biology | Year: 2010

Overexpression, genetic amplification and mutations of p21-activated kinase 4 (PAK4) were found in a variety of human cancers. PAK4 regulated actin cytoskeleton reorganization by phosphorylating LIMK1 and promoted cancer cells migration. Using yeast two-hybrid screen, we identified a novel PAK4 binding protein, DGCR6L, which was associated with cancer cell metastasis. We confirmed PAK4 binding to the DGCR6L specifically by GST pull-down assay, and found an association between endogenous PAK4 and DGCR6L by immunoprecipitation in mammalian cells. Furthermore, L115 of DGCR6L was the critical amino acid to bind 466-572aa in the very C-terminus of PAK4. Importantly, DGCR6L was required for the formation of PAK4-DGCR6L-β-actin complex. Overexpressed DGCR6L promoted migration of AGS cells mediated by PAK4, whereas knock-down of DGCR6L markedly inhibited the migration of those cells. Moreover, DGCR6L (L115V), which did not bind to PAK4, lost the ability to promote AGS cells migration. DGCR6L colocalized with PAK4 or F-actin and enhanced the phosphorylation level of LIMK1 and cofilin in a dose dependent manner. Taken together, our results demonstrated that DGCR6L, a novel PAK4 interacting protein, regulated PAK4-mediated migration of human gastric cancer cells via LIMK1. © 2009 Elsevier Ltd. All rights reserved.

Liu X.,Key Laboratory of Cell Biology | Wang Z.,Key Laboratory of Cell Biology | Wang R.,Key Laboratory of Cell Biology | Zhao F.,Key Laboratory of Cell Biology | And 3 more authors.
International Journal of Molecular Medicine | Year: 2013

Although transplantation of human mesenchymal stem cells (MSCs) derived from amnion (hAMSCs), bone marrow (hBMSCs) and adipose tissues (hADSCs) has been shown to aid in the repair of cutaneous wounds in mouse models, little information is available regarding the relative efficacy of MSCs from different sources. In this study, we compared their therapeutic potentials by transplanting equal numbers of hAMSCs, hBMSCs or hADSCs in a mouse model of cutaneous wounds. The results suggested that an hADSC injection has the most pronounced effect on wound closure. Histological evaluation showed enhanced re-epithelialization in the hADSC group compared with the hBMSC and hAMSC groups. Although there was a slight improvement in wound healing in the hAMSC and hBMSC groups, the differences between the groups were statistically insignificant. In a trans-well coculture model, wound healing migration and transwell migration assays showed that hADSCs were superior to hAMSCs and hBMSCs at promoting human dermal fibroblast (hDF) migration. However, there was no significant difference in fibroblast proliferation between the hAMSC, hBMSC and hADSC groups, as measured by WST assay. Our results also indicated that hDFs cocultured with hADSCs for 48 h signifi-cantly upregulated their mRNA expression of the cytokine vascular endothelial growth factor, basic fibroblast growth factor, keratinocyte growth factor and transforming growth factor-β and increased the mRNA and protein levels of type I collagen. Collectively, these data suggest that hADSCs are a potential source of MSCs for therapeutic healing in cutaneous wounds in terms of efficacy, accessibility and availability.

Xu Z.-R.,Northeastern University China | Yang C.-G.,Northeastern University China | Liu C.-H.,Northeastern University China | Zhou Z.,Key Laboratory of Cell Biology | And 2 more authors.
Talanta | Year: 2010

A novel microfluidic chip integrating an osmosis-based micro-pump was developed and used for perfusion cell culture. The micro-pump includes two sealed chambers, i.e., the inner osmotic reagent chamber and the outer water chamber, sandwiching a semi-permeable membrane. The water in the outer chamber was forced to flow through the membrane into the inner chamber via osmosis, facilitating continuous flow of fluidic zone in the channel. An average flow rate of 0.33 μL min-1 was obtained within 50 h along with a precision of 4.3% RSD (n = 51) by using a 100 mg mL-1 polyvinylpyrrolidone (PVP) solution as the osmotic driving reagent and a flow passage area of 0.98 cm2 of the semi-permeable membrane. The power-free micro-pump has been demonstrated to be pulse-free offering stable flow rates during long-term operation. The present microfluidic chip has been successfully applied for the perfusion culture of human colorectal carcinoma cell by continuously refreshing the culture medium with the osmotic micro-pump. In addition, in situ cell immunostaining was also performed on the microchip by driving all the reagent zones with the integrated micro-pump. © 2009 Elsevier B.V. All rights reserved.

Wei J.-Y.,Key Laboratory of Cell Biology | Lu Q.-N.,Key Laboratory of Cell Biology | Li W.-M.,Key Laboratory of Cell Biology | He W.,Key Laboratory of Cell Biology
Brain Research | Year: 2015

Histone deacetylase 5 (HDAC5) undergoes signal-dependent shuttling between the nucleus and cytoplasm, which is regulated in part by calcium/calmodulin-dependent kinase (CaMK)-mediated phosphorylation. Here, we report that HDAC5 regulates the survival of cortical neurons in pathological conditions. HDAC5 was evenly localized to the nucleus and cytoplasm in cultured cortical neurons. However, in response to 50 μM NMDA conditions that induced neuronal cell apoptosis, nuclear-distributed HDAC5 was rapidly phosphorylated and translocated into cytoplasm of the cultured cortical neurons. Treatment with a CaMKII inhibitor KN93 suppressed HDAC5 phosphorylation and nuclear translocation induced by NMDA, whereas constitutively active CaMKIIα (T286D) stimulated HDAC5 nuclear export. Importantly, we showed that ectopic expression of nuclear-localized HDAC5 in cortical neurons suppressed NMDA-induced apoptosis. Finally, inactivation of HDAC5 by treatment with the class II-specific HDAC inhibitor trichostatin A (TSA) promoted NMDA-induced neuronal cell apoptosis. Altogether, these data identify HDAC5 and its intracellular translocation as key effectors of multiple pathways that regulate neuronal cell apoptosis. © 2015 Elsevier B.V.

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