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author:("An, ligno")
1.  Genetic Determinants Involved in p-Aminosalicylic Acid Resistance in Clinical Isolates from Tuberculosis Patients in Northern China from 2006 to 2012 
p-Aminosalicylic acid (PAS) is an important compound for treating multidrug-resistant tuberculosis (TB). Previous studies showed that thyA mutations are often related to PAS resistance in clinical isolates. We performed a systematic analysis of isolate genotypes and detected mutations in three folate pathway genes (folC, thyA, and ribD) in 61.1% (127/208) of PAS-resistant isolates, including 11 double mutants. This result expands our knowledge about the distribution and frequency of mutations related to PAS resistance in mycobacterial clinical isolates.
PMCID: PMC4335845  PMID: 25421465
2.  SCARB2/LIMP-2 Regulates IFN Production of Plasmacytoid Dendritic Cells by Mediating Endosomal Translocation of TLR9 and Nuclear Translocation of IRF7 
Scavenger receptor class B, member 2 (SCARB2) is essential for endosome biogenesis and reorganization and serves as a receptor for both β-glucocerebrosidase and enterovirus 71. However, little is known about its function in innate immune cells. In this study, we show that, among human peripheral blood cells, SCARB2 is most highly expressed in plasmacytoid dendritic cells (pDCs), and its expression is further upregulated by CpG oligodeoxynucleotide stimulation. Knockdown of SCARB2 in pDC cell line GEN2.2 dramatically reduces CpG-induced type I IFN production. Detailed studies reveal that SCARB2 localizes in late endosome/lysosome of pDCs, and knockdown of SCARB2 does not affect CpG oligodeoxynucleotide uptake but results in the retention of TLR9 in the endoplasmic reticulum and an impaired nuclear translocation of IFN regulatory factor 7. The IFN-I production by TLR7 ligand stimulation is also impaired by SCARB2 knockdown. However, SCARB2 is not essential for influenza virus or HSV-induced IFN-I production. These findings suggest that SCARB2 regulates TLR9-dependent IFN-I production of pDCs by mediating endosomal translocation of TLR9 and nuclear translocation of IFN regulatory factor 7.
PMCID: PMC4506778  PMID: 25862818
3.  Characterization of species-specific genes regulated by E2-2 in human plasmacytoid dendritic cells 
Scientific Reports  2015;5:10752.
Dendritic cells (DCs) are sentinels of the immune system and comprise two distinct subsets: conventional DCs (cDCs) and plasmacytoid DCs (pDCs). Human pDCs are distinguished from mouse pDCs phenotypically and functionally. Basic helix-loop-helix protein E2-2 is defined as an essential transcription factor for mouse pDC development, cell fate maintenance and gene programe. It is unknown whether E2-2 regulation contributes to this species-specific difference. Here we investigated the function of E2-2 in human pDCs and screened human-specific genes regulated by E2-2. Reduced E2-2 expression in human pDC cell line GEN2.2 resulted in diminished IFN-α production in response to CpG but elevated antigen presentation capacity. Gene expression profiling showed that E2-2 silence down-regulated pDC signature genes but up-regulated cDC signature genes. Thirty human-specific genes regulated by E2-2 knockdown were identified. Among these genes, we confirmed that expression of Siglec-6 was inhibited by E2-2. Further more, Siglec-6 was expressed at a higher level on a human pDC subset with drastically lower expression of E2-2. Collectively, these results highlight that E2-2 modulates pDC function in a species-specific manner, which may provide insights for pDC development and functions.
PMCID: PMC4505321  PMID: 26182859
4.  Expression Quantitative Trait Loci for CARD8 Contributes to Risk of Two Infection-Related Cancers—Hepatocellular Carcinoma and Cervical Cancer 
PLoS ONE  2015;10(7):e0132352.
Caspase recruitment domain family, member 8 (CARD8) can coordinate innate and adaptive immune responses and sensitize cells to apoptosis, which may participate in tumorigenesis of virus-induced hepatocellular carcinoma (HCC) and cervical cancer. By bioinformatics analyses, we identified several single nucleotide polymorphisms (SNPs) within a new identified long non-coding RNA (lncRNA) as expression quantitative trait loci (eQTLs) for CARD8. In this study, we therefore hypothesized that CARD8 eQTLs SNPs within lncRNA may influence the risk of HCC and cervical cancer. We performed two independent case-control studies of 1,300 cases with HBV-positive HCC and 1,344 normal controls, together with 1,486 cervical cancer patients and 1,536 control subjects to test the association between eQTLs SNP (rs7248320) for CARD8 and the risk of HCC and cervical cancer. The variant genotype of rs7248320 was significantly associated with increased risk of HCC and cervical cancer [GG vs. AA/GA: adjusted odds ratio (OR) = 1.28, 95% confidence interval (CI) = 1.03–1.61, P = 0.028 for HCC; adjusted OR = 1.34, 95% CI = 1.09–1.66, P = 0.006 for cervical cancer]. Moreover, the effect of rs7248320 on cervical cancer risk was more prominent in premenopausal women. Further interactive analysis detected a significantly multiplicative interaction between rs7248320 and menopausal status on cervical cancer risk (P = 0.018). These findings suggest that CARD8 eQTLs SNP may serve as a susceptibility marker for virus-related HCC and cervical cancer.
PMCID: PMC4492972  PMID: 26147888
5.  Research on the Effect of Electrical Signals on Growth of Sansevieria under Light-Emitting Diode (LED) Lighting Environment 
PLoS ONE  2015;10(6):e0131838.
The plant electrical signal has some features, e.g. weak, low-frequency and time-varying. To detect changes in plant electrical signals, LED light source was used to create a controllable light environment in this study. The electrical signal data were collected from Sansevieria leaves under the different illumination conditions, and the data was analyzed in time domain, frequency domain and time–frequency domain, respectively. These analyses are helpful to explore the relationship between changes in the light environment and electrical signals in Sansevieria leaves. The changes in the plant electrical signal reflected the changes in the intensity of photosynthesis. In this study, we proposed a new method to express plant photosynthetic intensity as a function of the electrical signal. That is, the plant electrical signal can be used to describe the state of plant growth.
PMCID: PMC4487690  PMID: 26121469
6.  Adeno-Associated Virus Vector Mediated Delivery of the HBV Genome Induces Chronic Hepatitis B Virus Infection and Liver Fibrosis in Mice 
PLoS ONE  2015;10(6):e0130052.
Liver cirrhosis and hepatocellular carcinomas are major health problems of chronic hepatitis B virus (HBV) infection. To date, rare model has reproduced liver fibrosis associated with long-term HBV infection which in turn has hindered both the understanding of HBV biology and the development of new treatment options. Here, using adeno-associated virus serotype 8 (AAV8) mediated delivery of a 1.2-kb HBV genome, we successfully generated a chronic HBV infectious mouse model that presents the associated liver fibrosis observed following human infection. After AAV8/HBV1.2 vector administration, mice demonstrated effective HBV replication and transcription which resulted in HBV antigen expression and viremia over 6 months. Although no obvious acute inflammatory response was noted, these mice still developed chronic liver disease and hepatic fibrogenesis as demonstrated by increased ground glass-like hepatocytes, an increasing trend of collagen deposition and upregulated fibrosis markers, including type I collagen, type III collagen, tissue inhibitor of metalloproteinase (TIMP), and transforming growth factor-β1(TGF-β1). Taken together, AAV-mediated HBV gene delivery to the mouse liver, induced HBV persistent infection accompanied by liver fibrosis which can serve as a model for investigating the precise mechanisms underlying liver fibrosis following chronic HBV infection as well as for the potential development of novel therapeutics.
PMCID: PMC4468063  PMID: 26075890
7.  A Cross Structured Light Sensor and Stripe Segmentation Method for Visual Tracking of a Wall Climbing Robot 
Sensors (Basel, Switzerland)  2015;15(6):13725-13751.
In non-destructive testing (NDT) of metal welds, weld line tracking is usually performed outdoors, where the structured light sources are always disturbed by various noises, such as sunlight, shadows, and reflections from the weld line surface. In this paper, we design a cross structured light (CSL) to detect the weld line and propose a robust laser stripe segmentation algorithm to overcome the noises in structured light images. An adaptive monochromatic space is applied to preprocess the image with ambient noises. In the monochromatic image, the laser stripe obtained is recovered as a multichannel signal by minimum entropy deconvolution. Lastly, the stripe centre points are extracted from the image. In experiments, the CSL sensor and the proposed algorithm are applied to guide a wall climbing robot inspecting the weld line of a wind power tower. The experimental results show that the CSL sensor can capture the 3D information of the welds with high accuracy, and the proposed algorithm contributes to the weld line inspection and the robot navigation.
PMCID: PMC4507594  PMID: 26110403
structured light sensor; laser stripe segmentation; weld line tracking; wall climbing robot
8.  Juglone exerts antitumor effect in ovarian cancer cells 
Juglone is isolated from many species of the Juglandaceae family and used as an anti-viral, anti-bacterial, and anti-tumor therapeutic. Here, we evaluated juglone-induced antitumor effect in ovarian cancer SKOV3 cells.
Materials and Methods:
MTT assay was performed to examine juglone anti-proliferative effect. Cell cycle and apoptosis were studied using flow cytometry in juglone-treated SKOV3 cells. To investigate molecular mechanism of cell cycle and apoptosis, protein expression levels were measured by Western blot analysis of cyclin D1, Bcl-2, Bax, cytochrome c, caspase-9 and caspase-3. To investigate the motility of juglone-treated SKOV3 cell, Matrigel invasion assay was employed to characterize cell invasion. Also, matrix metalloproteinase-2 (MMP-2) expression levels were detected by western blot.
Juglone significantly inhibited SKOV3 cell proliferation as shown by G0/G1 phase arrest, and this effect was mediated by inactivation of cyclin D1 protein (P<0.05). Juglone induced apoptosis in SKOV3 cell which was accompanied by caspase-9 and caspase-3 activation (P<0.05). Juglone decreased Bcl-2 levels and increased Bax and cytochrome c (Cyt c) levels (P<0.05). Juglone sufficiently inhibited invasion while evidently decreased MMP-2 expression (P<0.05).
The results suggest that juglone could probably induce apoptosis through mitochondrial pathway and restrained cell invasiveness by decreasing MMP expression.
PMCID: PMC4509948  PMID: 26221477
Apoptosis; Cell cycle arrest; Invasion; Juglone; Ovarian cancer
9.  Hydrothermal Synthesis of Lanthanide Stannates Pyrochlore Nanocrystals for Catalytic Combustion of Soot Particulates 
The Scientific World Journal  2015;2015:254165.
Nanocrystalline La2Sn2O7 and La2Sn1.8Co0.2O7 with a phase-pure pyrochlore structure were synthesized by a hydrothermal method, and their catalytic activity was investigated for soot combustion. The as-synthesized catalysts presented relatively larger surface area, and pore volume, which was benefit to the gas molecule diffusion in the reaction. A uniform spherical structure with particle size of 200–500 nm was found in SEM. The samples via hydrothermal route are more active for catalytic soot combustion, ascribing to the spherical morphology, high surface area and improved oxygen mobility. After Co, the reducibility was improved and surface oxygen vacancy was produced, resulting in the enhanced activity and selectivity to CO2 formation.
PMCID: PMC4454749  PMID: 26090513
10.  Ocular syphilis: an alarming infectious eye disease 
Background: To describe the clinical manifestations and ancillary examination outcomes of ocular syphilis in Southeast China. Materials and methods: This is a retrospective, nonrandom case study. Demographic information, serum and cerebrospinal fluid (CSF) test results, and findings of fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), and spectral domain optical coherence tomography (SD-OCT) were analyzed. Results: The study examined 21 eyes of 13 patients (average age 50.3 ± 5.9 (range 37-61) years). HIV co-infection was found in one patient. The most common manifestation was chorioretinitis (52.4%). Disc hyperfluorescence (66.7%) and persistent dark spots (91.7%) were the most common findings on FFA and ICGA, respectively. The inner segment/outer segment junction (IS/OS) loss was the most frequent manifestation (86.7%). Among the six patients with confirmed neurosyphilis, the average CSF protein level was 528.8 ± 327.1 mg/L. Visual acuity (VA) was improved in 8 of 13 eyes (61.5%) after treatment. Conclusions: The manifestations of ocular syphilis can mimic any eye disease. Chorioretinitis was the most common finding in this case series. “Leopard spots” was the characteristic manifestation on FFA. IS/OS loss was the most common finding in patients with posterior uveitis on SD-OCT. Lumbar puncture can contribute to the diagnosis of neurosyphilis. Treatment for ocular syphilis was effective in these patients.
PMCID: PMC4509273  PMID: 26221328
Chorioretinitis; CSF; FFA; ICGA; neurosyphilis; ocular syphilis; syphilis; SD-OCT
11.  Jingtong Granule: A Chinese Patent Medicine for Cervical Radiculopathy 
Objective. This paper systematically assessed the efficacy and safety of Jingtong granule (JG) for cervical radiculopathy (CR). Methods. Randomized controlled trials comparing JG with no intervention, placebo, or conventional therapies were retrieved. The trials testing JG combined with conventional therapies versus conventional therapies were also enrolled. Study selection, methodological assessment, data extraction, and analysis were conducted in accordance with the Cochrane standards. The strength of evidence was evaluated according to GRADE approach. Results. Three trials with 400 participants were included. Methodological quality was evaluated as generally low. One study found that JG showed significant difference on decreasing pain scores compared with placebo. Meta-analysis indicated that JG plus conventional analgesic exhibited a significant immediate effect on the pain scores (WMD = 1.63; 95% CI: 1.29 to 1.98; P < 0.00001). Additionally, JG combined with analgesic presented beneficial immediate effect on neck disability index. However, the treatment effects of JG demonstrated in the trials were not large, and the safety of JG was unproven. Finally the evidence level was evaluated to be low. Conclusions. Our results indicated that JG showed some potential benefits for CR. Nevertheless, treatment effects are uncertain due to both the methodological concerns and the very modest reported improvements.
PMCID: PMC4443761  PMID: 26064154
12.  The cistrome and gene signature of androgen receptor splice variants in castration-resistant prostate cancer cells 
The Journal of urology  2014;193(2):690-698.
Spliced variant forms of androgen receptor (AR-Vs) have been identified recently in castration-resistant prostate cancer (CRPC) cell lines and clinical samples. We identified the cistrome and gene signature of AR-Vs in CRPC cell lines and determined the clinical significance of AR-Vs regulated genes.
Materials and Methods
The CRPC cell line 22Rv1, which expresses both full length androgen receptor (AR-FL) and AR-Vs endogenously, was used as the research model. We established 22Rv1-ARFL−/ARVs+ and 22Rv1- ARFL−/ARVs− through RNA interference. ChIP-seq and microarray techniques were used to identify cistrome and gene expression profiles of AR-Vs in the absence of androgen.
AR-Vs binding sites were identified in 22Rv1-ARFL−/ARVs+. A set of genes was found to be regulated uniquely by AR-Vs, but not by full-length AR in the absence of androgen. Integrated analysis revealed that some genes are modulated by AR-Vs directly. Unsupervised clustering analysis showed that the AR-Vs gene signature can differentiate not only benign from malignant prostate tissue, but also localized prostate cancer from metastatic CRPC specimens. Some genes that were modulated uniquely by AR-Vs also correlated with histological grade and biochemical failure.
We conclude that AR-Vs can bind to DNA independently of full-length AR in the absence of androgen and modulate a unique set of genes that is not regulated by AR-FL. The AR-Vs gene signature correlates with disease progression, and distinguishes between primary cancer and CRPC specimens, as well as benign and malignant prostate specimens.
PMCID: PMC4411637  PMID: 25132238
Prostatic Neoplasms; Castration-Resistant; Receptors; Androgen; Alternative Splicing; Cistrome; Gene signature
13.  CrossMap: a versatile tool for coordinate conversion between genome assemblies 
Bioinformatics  2013;30(7):1006-1007.
Motivation: Reference genome assemblies are subject to change and refinement from time to time. Generally, researchers need to convert the results that have been analyzed according to old assemblies to newer versions, or vice versa, to facilitate meta-analysis, direct comparison, data integration and visualization. Several useful conversion tools can convert genome interval files in browser extensible data or general feature format, but none have the functionality to convert files in sequence alignment map or BigWig format. This is a significant gap in computational genomics tools, as these formats are the ones most widely used for representing high-throughput sequencing data, such as RNA-seq, chromatin immunoprecipitation sequencing, DNA-seq, etc.
Results: Here we developed CrossMap, a versatile and efficient tool for converting genome coordinates between assemblies. CrossMap supports most of the commonly used file formats, including BAM, sequence alignment map, Wiggle, BigWig, browser extensible data, general feature format, gene transfer format and variant call format.
Availability and implementation: CrossMap is written in Python and C. Source code and a comprehensive user’s manual are freely available at:
Contact: or
Supplementary information: Supplementary data are available at Bioinformatics online.
PMCID: PMC3967108  PMID: 24351709
14.  CBP loss cooperates with PTEN haploinsufficiency to drive prostate cancer: implications for epigenetic therapy 
Cancer research  2014;74(7):2050-2061.
Despite the high incidence and mortality of prostate cancer, the etiology of this disease is not fully understood. In this study, we develop functional evidence for CBP and PTEN interaction in prostate cancer based on findings of their correlate expression in the human disease. Cbppc−/−;Ptenpc+/− mice exhibited higher cell proliferation in the prostate and an early onset of high-grade prostatic intraepithelial neoplasia. Levels of EZH2 methyltransferase were increased along with its Thr350 phosphorylation in both mouse Cbp−/−;Pten+/− and human prostate cancer cells. CBP loss and PTEN deficiency cooperated to trigger a switch from K27-acetylated histone H3 to K27-trimethylated bulk histones, in a manner associated with decreased expression of the growth inhibitory EZH2 target genes DAB2IP, p27KIP1 and p21CIP1. Conversely, treatment with the histone deacetylase inhibitor panobinostat reversed this switch, in a manner associated with tumor suppression in Cbppc−/−;Ptenpc+/− mice. Our findings show how CBP and PTEN interact to mediate tumor suppression in the prostate, establishing a central role for histone modification in the etiology of prostate cancer and providing a rationale for clinical evaluation of epigenetic targeted therapy in prostate cancer patients.
PMCID: PMC3975662  PMID: 24491799
CBP; PTEN; EZH2; histone; acetylation; methylation; epigenetics; targeted therapy; prostate cancer
15.  Human BDCA2+CD123+CD56+ dendritic cells (DCs) related to blastic plasmacytoid dendritic cell neoplasm represent a unique myeloid DC subset 
Protein & Cell  2015;6(4):297-306.
Dendritic cells (DCs) comprise two functionally distinct subsets: plasmacytoid DCs (pDCs) and myeloid DCs (mDCs). pDCs are specialized in rapid and massive secretion of type I interferon (IFN-I) in response to nucleic acids through Toll like receptor (TLR)-7 or TLR-9. In this report, we characterized a CD56+ DC population that express typical pDC markers including CD123 and BDCA2 but produce much less IFN-I comparing with pDCs. In addition, CD56+ DCs cluster together with mDCs but not pDCs by genome-wide transcriptional profiling. Accordingly, CD56+ DCs functionally resemble mDCs by producing IL-12 upon TLR4 stimulation and priming naïve T cells without prior activation. These data suggest that the CD56+ DCs represent a novel mDC subset mixed with some pDC features. A CD4+CD56+ hematological malignancy was classified as blastic plasmacytoid dendritic cell neoplasm (BPDCN) due to its expression of characteristic molecules of pDCs. However, we demonstrated that BPDCN is closer to CD56+ DCs than pDCs by global gene-expression profiling. Thus, we propose that the CD4+CD56+ neoplasm may be a tumor counterpart of CD56+ mDCs but not pDCs.
Electronic supplementary material
The online version of this article (doi:10.1007/s13238-015-0140-x) contains supplementary material, which is available to authorized users.
PMCID: PMC4383756  PMID: 25779340
dendritic cells; CD56+ DC; pDC; mDC; BPDCN
16.  Human BDCA2+CD123+CD56+ dendritic cells (DCs) related to blastic plasmacytoid dendritic cell neoplasm represent a unique myeloid DC subset 
Protein & Cell  2015;6(4):297-306.
Dendritic cells (DCs) comprise two functionally distinct subsets: plasmacytoid DCs (pDCs) and myeloid DCs (mDCs). pDCs are specialized in rapid and massive secretion of type I interferon (IFN-I) in response to nucleic acids through Toll like receptor (TLR)-7 or TLR-9. In this report, we characterized a CD56+ DC population that express typical pDC markers including CD123 and BDCA2 but produce much less IFN-I comparing with pDCs. In addition, CD56+ DCs cluster together with mDCs but not pDCs by genome-wide transcriptional profiling. Accordingly, CD56+ DCs functionally resemble mDCs by producing IL-12 upon TLR4 stimulation and priming naïve T cells without prior activation. These data suggest that the CD56+ DCs represent a novel mDC subset mixed with some pDC features. A CD4+CD56+ hematological malignancy was classified as blastic plasmacytoid dendritic cell neoplasm (BPDCN) due to its expression of characteristic molecules of pDCs. However, we demonstrated that BPDCN is closer to CD56+ DCs than pDCs by global gene-expression profiling. Thus, we propose that the CD4+CD56+ neoplasm may be a tumor counterpart of CD56+ mDCs but not pDCs.
Electronic supplementary material
The online version of this article (doi:10.1007/s13238-015-0140-x) contains supplementary material, which is available to authorized users.
PMCID: PMC4383756  PMID: 25779340
dendritic cells; CD56+ DC; pDC; mDC; BPDCN
17.  The G-protein Alpha Subunit Gsα Is A Tumor Suppressor In Sonic Hedgehog-driven Medulloblastoma 
Nature medicine  2014;20(9):1035-1042.
Medulloblastoma, the most common malignant childhood brain tumor, exhibits distinct molecular subtypes and cellular origins. Genetic alterations driving medulloblastoma initiation and progression remain poorly understood. Herein, we identify GNAS, encoding the G-protein Gsα, as a potent tumor suppressor gene that defines a subset of aggressive Sonic Hedgehog (Shh)-driven human medulloblastomas. Ablation of the single Gnas gene in anatomically-distinct progenitors is sufficient to induce Shh-associated medulloblastomas, which recapitulate their human counterparts. Gsα is highly enriched at the primary cilium of granule neuron precursors and suppresses Shh-signaling by regulating both the cAMP-dependent pathway and ciliary trafficking of Hedgehog pathway components. Elevation of a Gsα effector, cAMP, effectively inhibits tumor cell proliferation and progression in Gnas mutants. Thus, our gain- and loss-of-function studies identify a previously unrecognized tumor suppressor function for Gsα that acts as a molecular link across Shh-group medulloblastomas of disparate cellular and anatomical origins, illuminating G-protein modulation as a potential therapeutic avenue.
PMCID: PMC4334261  PMID: 25150496
medulloblastoma; G-protein; cAMP; GPCR; cell lineage; sonic hedgehog signaling; cilia; cellular origins
18.  Molecular cloning and expression analysis of RrNHX1 and RrVHA-c genes related to salt tolerance in wild Rosa rugosa 
Salt stress is one important factor influencing the growth and development of plants, and salt tolerance of plants is a result of combined action of multiple genes and mechanisms. Rosa rugosa is not only an important ornamental plant, but also the natural aromatic plant of high value. Wild R. rugosa which is naturally distributed on the coast and islands of China has a good salt tolerance due to the special living environment. Here, the vacuolar Na+/H+ reverse transporter gene (NHX1) and the vacuolar H+-ATPase subunit C gene (VHA-c) closely related to plant salt tolerance were isolated from wild R. rugosa, and the expression patterns in R. rugosa leaves of the two genes under NaCl stress were determined by real-time quantitative fluorescence PCR. The results showed that the RrNHX1 protein is a constitutive Na+/H+ reverse transporter, the expression of the RrNHX1 gene first increased and then decreased with the increasing salt concentration, and had a time-controlled effect. The RrVHA-c gene is suggestive of the housekeeping feature, its expression pattern showed a similar variation trend with the RrNHX1 gene under the stress of different concentrations of NaCl, and its temporal expression level under 200 mM NaCl stress presented bimodal change. These findings indicated that RrNHX1 and RrVHA-c genes are closely associated with the salt tolerance trait of wild R. rugosa.
PMCID: PMC4487260  PMID: 26150747
Wild R. rugosa; Salt tolerance; Vacuolar Na+/H+ reverse transporter; Vacuolar H+-ATPase; Gene cloning and expression
19.  CD147 modulates autophagy through the PI3K/Akt/mTOR pathway in human prostate cancer PC-3 cells 
Oncology Letters  2015;9(3):1439-1443.
The multifunctional glycoprotein cluster of differentiation (CD)147 is highly expressed on the cell surface of the majority of cancer cells, and promotes tumor invasion, metastasis and growth. However, the role of CD147 in autophagy has not yet been explored in prostrate cancer cells. In the present study, prostate cancer PC-3 cells were cultured under starvation conditions, and the expression level of CD147 gradually increased. Therefore, RNA interference was used to inhibit CD147 expression, in order to investigate the biological role of this glycoprotein in autophagy progression. Autophagic activity was monitored by the changes in green fluorescent protein-light chain 3 (GFP-LC3) location and the expression of the autophagy-associated protein LC3-II. It was found that downregulation of CD147 significantly promoted GFP-LC3 puncta formation and the expression of LC3-II. Furthermore, the levels of phosphorylated serine/threonine protein kinase B (p-Akt) and phosphorylated mammalian target of rapamycin (p-mTOR) were significantly decreased, and the level of LC3-II was inversely associated with levels of p-Akt and p-mTOR in cells with downregulated expression of CD147. The results of a trypan blue exclusion assay revealed that starvation-induced cell death was increased in PC-3/shCD147 cells compared with control PC-3/Scramble cells (37.7±6.4 vs. 21.7±5.5%). Together, these results indicate that CD147 may be important in the inhibition of autophagy via the PI3K/Akt/mTOR pathway, which prevents cell death from unrestrained autophagy.
PMCID: PMC4315002  PMID: 25663928
cluster of differentiation 147; autophagy; prostate cancer; PI3K/Akt/mTOR pathway
20.  AtDsPTP1 acts as a negative regulator in osmotic stress signalling during Arabidopsis seed germination and seedling establishment 
Journal of Experimental Botany  2014;66(5):1339-1353.
AtDsPTP1 was found to regulate ABA accumulation and act as a negative regulator in osmotic stress signalling during Arabidospsis seed germination and seedling establishment.
Dual-specificity protein phosphatases (DsPTPs) target both tyrosine and serine/threonine residues and play roles in plant growth and development. We have characterized an Arabidopsis mutant, dsptp1, which shows a higher seed germination rate and better root elongation under osmotic stress than the wild type. By contrast, its overexpression line, DsPTP1-OE, shows inhibited seed germination and root elongation; and its complemented line, DsPTP1-Com, resembles the wild type and rescues DsPTP1-OE under osmotic stress. Expression of AtDsPTP1 is enhanced by osmotic stress in seed coats, bases of rosette leaves, and roots. Compared with the wild type, the dsptp1 mutant shows increased proline accumulation, reduced malondialdehyde (MDA) content and ion leakage, and enhanced antioxidant enzyme activity in response to osmotic stress. AtDsPTP1 regulates the transcript levels of various dehydration-responsive genes under osmotic stress. Abscisic acid (ABA) accumulation in dsptp1 under osmotic stress is reduced with reduced expression of the ABA-biosynthesis gene NCED3 and increased expression of the ABA-catabolism gene CYP707A4. AtDsPTP1 also regulates the expression of key components in the ABA-signalling pathway. In conclusion, AtDsPTP1 regulates ABA accumulation, and acts as a negative regulator in osmotic stress signalling during Arabidospsis seed germination and seedling establishment.
PMCID: PMC4339596  PMID: 25540435
Abscisic acid (ABA); Arabidopsis; dual-specificity protein phosphatase; osmotic stress; root elongation; seed germination.
21.  HIV-1 immunopathogenesis in humanized mouse models 
Science China. Life sciences  2010;53(2):195-203.
In recent years, the technology of constructing chimeric mice with humanized immune systems has markedly improved. Multiple lineages of human immune cells develop in immunodeficient mice that have been transplanted with human hematopoietic stem cells. More importantly, these mice mount functional humoral and cellular immune responses upon immunization and microbial infection. Human immunodeficiency virus type I (HIV-1) can establish an infection in humanized mice, resulting in CD4+ T-cell depletion and an accompanying nonspecific immune activation, which mimics the immunopathology in HIV-1-infected human patients. This makes humanized mice an optimal model for studying the mechanisms of HIV-1 immunopathogenesis and for developing novel immune-based therapies.
PMCID: PMC4224686  PMID: 20596827
22.  Epidaurus: aggregation and integration analysis of prostate cancer epigenome 
Nucleic Acids Research  2014;43(2):e7.
Integrative analyses of epigenetic data promise a deeper understanding of the epigenome. Epidaurus is a bioinformatics tool used to effectively reveal inter-dataset relevance and differences through data aggregation, integration and visualization. In this study, we demonstrated the utility of Epidaurus in validating hypotheses and generating novel biological insights. In particular, we described the use of Epidaurus to (i) integrate epigenetic data from prostate cancer cell lines to validate the activation function of EZH2 in castration-resistant prostate cancer and to (ii) study the mechanism of androgen receptor (AR) binding deregulation induced by the knockdown of FOXA1. We found that EZH2's noncanonical activation function was reaffirmed by its association with active histone markers and the lack of association with repressive markers. More importantly, we revealed that the binding of AR was selectively reprogramed to promoter regions, leading to the up-regulation of hundreds of cancer-associated genes including EGFR. The prebuilt epigenetic dataset from commonly used cell lines (LNCaP, VCaP, LNCaP-Abl, MCF7, GM12878, K562, HeLa-S3, A549, HePG2) makes Epidaurus a useful online resource for epigenetic research. As standalone software, Epidaurus is specifically designed to process user customized datasets with both efficiency and convenience.
PMCID: PMC4333365  PMID: 25378314
23.  Activation of p53 Transcriptional Activity by SMRT: a Histone Deacetylase 3-Independent Function of a Transcriptional Corepressor 
Molecular and Cellular Biology  2014;34(7):1246-1261.
The silencing mediator of retinoic acid and thyroid hormone receptors (SMRT) is an established histone deacetylase 3 (HDAC3)-dependent transcriptional corepressor. Microarray analyses of MCF-7 cells transfected with control or SMRT small interfering RNA revealed SMRT regulation of genes involved in DNA damage responses, and the levels of the DNA damage marker γH2AX as well as poly(ADP-ribose) polymerase cleavage were elevated in SMRT-depleted cells treated with doxorubicin. A number of these genes are established p53 targets. SMRT knockdown decreased the activity of two p53-dependent reporter genes as well as the expression of p53 target genes, such as CDKN1A (which encodes p21). SMRT bound directly to p53 and was recruited to p53 binding sites within the p21 promoter. Depletion of GPS2 and TBL1, components of the SMRT corepressor complex, but not histone deacetylase 3 (HDAC3) decreased p21-luciferase activity. p53 bound to the SMRT deacetylase activation domain (DAD), which mediates HDAC3 binding and activation, and HDAC3 could attenuate p53 binding to the DAD region of SMRT. Moreover, an HDAC3 binding-deficient SMRT DAD mutant coactivated p53 transcriptional activity. Collectively, these data highlight a biological role for SMRT in mediating DNA damage responses and suggest a model where p53 binding to the DAD limits HDAC3 interaction with this coregulator, thereby facilitating SMRT coactivation of p53-dependent gene expression.
PMCID: PMC3993559  PMID: 24449765
24.  Dielectrophoresis for Bioparticle Manipulation 
As an ideal method to manipulate biological particles, the dielectrophoresis (DEP) technique has been widely used in clinical diagnosis, disease treatment, drug development, immunoassays, cell sorting, etc. This review summarizes the research in the field of bioparticle manipulation based on DEP techniques. Firstly, the basic principle of DEP and its classical theories are introduced in brief; Secondly, a detailed introduction on the DEP technique used for bioparticle manipulation is presented, in which the applications are classified into five fields: capturing bioparticles to specific regions, focusing bioparticles in the sample, characterizing biomolecular interaction and detecting microorganism, pairing cells for electrofusion and separating different kinds of bioparticles; Thirdly, the effect of DEP on bioparticle viability is analyzed; Finally, the DEP techniques are summarized and future trends in bioparticle manipulation are suggested.
PMCID: PMC4227216  PMID: 25310652
dielectrophoresis; lab-on-a-chip; bioparticle; trapping; detection; focusing; pairing; separation
25.  MACE: model based analysis of ChIP-exo 
Nucleic Acids Research  2014;42(20):e156.
Understanding the role of a given transcription factor (TF) in regulating gene expression requires precise mapping of its binding sites in the genome. Chromatin immunoprecipitation-exo, an emerging technique using λ exonuclease to digest TF unbound DNA after ChIP, is designed to reveal transcription factor binding site (TFBS) boundaries with near-single nucleotide resolution. Although ChIP-exo promises deeper insights into transcription regulation, no dedicated bioinformatics tool exists to leverage its advantages. Most ChIP-seq and ChIP-chip analytic methods are not tailored for ChIP-exo, and thus cannot take full advantage of high-resolution ChIP-exo data. Here we describe a novel analysis framework, termed MACE (model-based analysis of ChIP-exo) dedicated to ChIP-exo data analysis. The MACE workflow consists of four steps: (i) sequencing data normalization and bias correction; (ii) signal consolidation and noise reduction; (iii) single-nucleotide resolution border peak detection using the Chebyshev Inequality and (iv) border matching using the Gale-Shapley stable matching algorithm. When applied to published human CTCF, yeast Reb1 and our own mouse ONECUT1/HNF6 ChIP-exo data, MACE is able to define TFBSs with high sensitivity, specificity and spatial resolution, as evidenced by multiple criteria including motif enrichment, sequence conservation, direct sequence pileup, nucleosome positioning and open chromatin states. In addition, we show that the fundamental advance of MACE is the identification of two boundaries of a TFBS with high resolution, whereas other methods only report a single location of the same event. The two boundaries help elucidate the in vivo binding structure of a given TF, e.g. whether the TF may bind as dimers or in a complex with other co-factors.
PMCID: PMC4227761  PMID: 25249628

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