Publications by authors named "Qian Bi"

20 Publications

  • Page 1 of 1

MDM2 Binding Protein Induces the Resistance of Hepatocellular Carcinoma Cells to Molecular Targeting Agents Enhancing the Transcription Factor Activity of the Pregnane X Receptor.

Front Oncol 2021 24;11:715193. Epub 2021 Jun 24.

Endoscopy Center, Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.

The MDM2 binding protein (MTBP) has been considered an important regulator of human malignancies. In this study, we demonstrate that the high level of MTBP's endogenous expression is correlated with poor prognosis of advanced hepatocellular carcinoma (HCC) patients who received sorafenib. MTBP interacted with the Pregnane X receptor (PXR) and enhanced the transcription factor activity of PXR. Moreover, MTBP enhanced the accumulation of PXR in HCC cells' nuclear and the recruitment of PXR to its downstream gene's () promoter region. Mechanically, the knockdown of MTBP in MHCC97-H cells with high levels of MTBP decelerated the clearance or metabolism of sorafenib in HCC cells and led to the resistance of HCC cells to sorafenib. Whereas overexpression of MTBP in in MHCC97-L cells with low levels of MTBP showed the opposite trend. By establishing the interaction between MTBP and PXR, our results indicate that MTBP could function as a co-activator of PXR and could be a promising therapeutic target to enhance the sensitivity of HCC cells to molecular targeting agents.
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http://dx.doi.org/10.3389/fonc.2021.715193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264664PMC
June 2021

Circadian misalignment leads to changes in cortisol rhythms, blood biochemical variables and serum miRNA profiles.

Biochem Biophys Res Commun 2021 Aug 12;567:9-16. Epub 2021 Jun 12.

State Key Laboratory of Biocontrol, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510006, China. Electronic address:

The circadian clock plays a critical role in synchronizing the inner molecular, metabolic and physiological processes to environmental cues that cycle with a period of 24 h. Non-24 h and shift schedules are commonly used in maritime operations, and both of which can disturb circadian rhythms. In this study, we first conducted an experiment in which the volunteers followed a 3-d rotary schedule with consecutive shift in sleep time (rotatory schedule), and analyzed the changes in salivary cortisol rhythms and blood variables. Next we conducted another experiment in which the volunteers followed an 8 h-on and 4-h off schedule (non-24-h schedule) to compare the changes in blood/serum variables. The rotatory schedule led to elevated levels of serum cortisol during the early stage, and the phase became delayed during the early and late stages. Interestingly, both of the schedules caused comprehensive changes in blood/serum biochemical variables and increased phosphate levels. Furthermore, transcriptomic analysis of the plasma miRNAs from the volunteers following the rotatory schedule identified a subset of serum miRNAs targeting genes involved in circadian rhythms, sleep homeostasis, phosphate transport and multiple important physiological processes. Overexpression of miRNAs targeting the phosphate transport associated genes, SLC20A1 and SLC20A2, showed altered expression due to rotary schedule resulted in attenuated cellular levels of phosphate, which might account for the changed levels in serum phosphate. These findings would further our understanding of the deleterious effects of shift schedules and help to optimize and enhance the performances and welfare of personnel working on similar schedules.
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http://dx.doi.org/10.1016/j.bbrc.2021.06.015DOI Listing
August 2021

Gastric peroral endoscopic pyloromyotomy versus gastric electrical stimulation in the treatment of refractory gastroparesis: methodologic issues.

Authors:
Yaqi Zhai Qian Bi

Endoscopy 2020 08 28;52(8):711. Epub 2020 Jul 28.

Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, China.

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http://dx.doi.org/10.1055/a-1176-1399DOI Listing
August 2020

Pharmacological and metagenomics evidence of polysaccharide from Polygonum multiflorum in the alleviation of insulin resistance.

Int J Biol Macromol 2020 Dec 17;164:1070-1079. Epub 2020 Jul 17.

College of Pharmaceutical Science, Yunnan University of Chinese Medicine, Kunming 650500, China. Electronic address:

Total polysaccharide from Polygonum multiflorum (PS) and 2,3,5,4'-tetrahydroxy-stilbene-2-O-β-D-glucoside (TSG) could relieve high-fat and high-sugar diet (HF-HSD) induced rats' insulin resistance (IR) by gut microbiota and host regulation. We found that PS and TSG significantly reversed the increase of fasting blood glucose and the decrease of glucose tolerance in HF-HSD induced IR rats. PS and TSG effectively reversed the imbalance of Firmicutes/Bacteroides caused by an HF-HSD, and significantly reduced the relative abundance of Proteobacteria. It also affected the functional genes of gut microbiota and regulated short-chain fatty acids (SCFAs) and its downstream signal protein molecules. Together, these results indicated that PS and TSG alleviated HF-HSD induced IR by promoting gut microbiota and host function. Thus, PS and TSG may be promising lead substances for developing IR inhibitors that could regulate gut microbiota and its molecular messenger SCFAs to remedy IR.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.07.085DOI Listing
December 2020

Water extract from processed Polygonum multiflorum modulate gut microbiota and glucose metabolism on insulin resistant rats.

BMC Complement Med Ther 2020 Apr 5;20(1):107. Epub 2020 Apr 5.

College of Pharmaceutical Science, Yunnan University of Traditional Chinese Medicine, 1076 Yuhua Road, Chenggong District, Kunming, Yunnan Province, People's Republic of China.

Background: The incidence of insulin resistance (IR) has rapidly increased worldwide over the last 20 years, no perfect solution has yet been identified. Finding new therapeutic drugs will help improve this situation. As a traditional Chinese medicine, PPM (processed Polygonum multiflorum) has widely been used in the clinic. Recently, other clinical functions of PPM have been widely analyzed.

Results: Administration of the water extract from PPM decreased the level of FBG, TC, and TG, and increased the level of FGC, thereby reducing the IR index and improving IR. Furthermore, Western blot analysis revealed that PPM significantly increased GPR43 and AMPK expression when compared with the MOD group, and GPR43, AMPK were known as glucose metabolism-related proteins. In addition, treatment with PPM can restore the balance of gut microbiota by adjusting the relative abundance of bacteria both at the phylum and genus level, and these changes have been reported to be related to IR.

Methods: Sprague Dawley (SD) rats were fed a high-fat diet and were gavaged daily with either normal saline solution or PPM for 12 weeks. Major biochemical indexes, such as fasting blood glucose (FBG), fasting glucagon (FGC), total cholesterol (TC), and triglyceride (TG) were measured. Then the protein expression of adenosine 5'-monophosphate -activated protein kinase (AMPK) and G protein-coupled receptor 43 (GPR43) was evaluated by using Western blot analysis. Moreover, the composition of gut microbiota was assessed by analyzing 16S rRNA sequences.

Conclusions: Our findings showed that PPM reversed the increasing of FBG and the decreasing of IRI, PPM accelerated the expression of glucose metabolism-related proteins and regulated the intestinal microecological balance. Therefore, we hold the opinion that PPM may be an effective option for treating IR.
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http://dx.doi.org/10.1186/s12906-020-02897-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132990PMC
April 2020

Polysaccharides from Polygonatum kingianum improve glucose and lipid metabolism in rats fed a high fat diet.

Biomed Pharmacother 2020 May 3;125:109910. Epub 2020 Feb 3.

College of Pharmaceutical Science, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China. Electronic address:

Objective: Polygonatum kingianum is a traditional Chinese medicine commonly used to treat diabetes and hyperlipidemia. Polysaccharides from Polygonatum kingianum could regulate glucose and lipid metabolism in high-fat diet (HFD) rats.

Methods: The gel permeation chromatography (GPC), liquid chromatography (HPLC) and chemical analysis were used to determine the molecular weight, monosaccharide composition, protein, polysaccharide and uronic acid content of the polysaccharide from Polygonatum kingianum, respectively. Total (PS) and high molecular weight (PSF) polysaccharides (> 100 KDa) were isolated and treated HFD rats for a 14-week period. TC, TG contents in blood samples were measured every two weeks, and HDL-C, LDL-C was measured at 12 and 14 weeks evaluating of blood lipids regulation activity of polysaccharide. The stool samples were used for 16S rDNA V4 highly variable region measurement method to regulate the role of polysaccharide in the intestinal microflora. The content of short chain fatty acid (SCFAs) in faeces was determined by gas chromatography (GC) to investigate the effect of polysaccharides on the content of SCFAs in the intestinal tract of rats. The expression of tight junction protein ZO-1 and occludin of intestinal tissue, and detection of the key protein expression in the LPS-TLR4/NFκB signaling pathway were detected by Western blot technique.

Results: We found that PS and PSF improved both diabetic symptoms and lipid metabolism. PS and PSF also modulated the gut microbiota composition, abundance and diversity of HFD rats, increased the relative abundance of short chain fatty acid (SCFA) producing bacteria and increased SCFA production, reduced intestinal permeability, relieved gastrointestinal inflammation, and improved lipid metabolism.

Conclusion: Polygonatum kingianum polysaccharides regulated the abundance and diversity of the intestinal microbial community through increasing the relative abundance of SCFA-producing bacteria. This promotes recovery of the intestinal permeability barrier, inhibits LPS entry into the circulation, alleviates inflammation, and prevents glucose and lipid metabolic disorders.
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http://dx.doi.org/10.1016/j.biopha.2020.109910DOI Listing
May 2020

Efficiently Capturing Mitochondria-Targeted Constituents with Hepatoprotective Activity from Medicinal Herbs.

Oxid Med Cell Longev 2019 9;2019:4353791. Epub 2019 Apr 9.

College of Pharmaceutical Science, Yunnan University of Traditional Chinese Medicine, 1076 Yuhua Road, Kunming, 650500 Yunnan Province, China.

Targeting mitochondria as a hepatic-protective strategy has gained attention, because of their important roles in energy production, adjustment of apoptosis, and generation of reactive oxygen species. To promote the discovery of natural mitochondria-targeted hepatic-protectants, we established a hepatocellular mitochondria-based capturing method by coupling affinity ultrafiltration with liquid chromatography/mass spectrometry (LC/MS), which is suitable for identifying mitochondrial ligands from medicinal herbs (MHs). After evaluating the feasibility of the method, it was applied for capturing mitochondria-targeting constituents from Peucedani Radix extract. A total of 10 active compounds were identified by LC/MS, all of which were newly identified mitochondrial ligands. The mitochondria-remedying activity of 4 of the 10 hits was confirmed by pharmacological tests . Additionally, the hepatic-protective abilities of 4 hits were verified in both carbon tetrachloride-damaged liver L02 cells and mice. These results indicated that the method could be used for identifying hepatic mitochondria-targeting constituents in MHs, which might be beneficial for hepatic-protective development.
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http://dx.doi.org/10.1155/2019/4353791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481013PMC
December 2019

Fast Switching Properties and Ion Diffusion Behavior of Polytriphenylamine Derivative with Pendent Ionic Liquid Unit.

ACS Appl Mater Interfaces 2018 Sep 17;10(38):32404-32412. Epub 2018 Sep 17.

International Sci. & Tech. Cooperation Base of Energy Materials and Application, College of Chemical Engineering , Zhejiang University of Technology , Hangzhou 310014 , P. R. China.

A novel triphenylamine derivative-linked ionic liquid unit, 1-(6-((4-(bis(4-(thiophen-2-yl)phenyl)amino)benzoyl)oxy)hexyl)-3-methyl-imidazolium tetrafluoroborate (TTPACIL-BF), was designed and synthesized successfully, and its corresponding polymer PTTPACIL-BF was obtained by the electropolymerization method. The highest occupied molecular orbital energy band of TTPACIL-BF is higher and the onset oxidative potential lower compared with that of 6-bromohexyl 4-(bis(4-(thiophen-2-yl)phenyl)amino) benzoate (TTPACBr) without modifying the ionic liquid unit. Both PTTPACIL-BF and PTTPACBr show similar color change and optical contrast under different redox states. However, PTTPACIL-BF presents a faster electrochromic switching time than PTTPACBr owing to the improved ionic conductivity and ion diffusion coefficient with the introduction of a pendent ionic liquid unit. It is more intriguing that PTTPACIL-BF could show electrochromism under different potentials even without supplying any additional electrolyte. The particular behavior further proves that BF ions around imidazole cations at the side chain may participate in balancing the charge of the polymer backbone when redox reaction happens, resulting in faster movement of ions during the doping process. The results imply that introducing an ionic liquid unit to the side chain is an efficient method to improve the switching time of conjugated polymers and would be inspirational for the design and preparation of novel bifunctional electrochromic polymeric electrolytes.
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http://dx.doi.org/10.1021/acsami.8b09878DOI Listing
September 2018

Volatile Oil from Amomi Fructus Attenuates 5-Fluorouracil-Induced Intestinal Mucositis.

Front Pharmacol 2017 9;8:786. Epub 2017 Nov 9.

College of Pharmaceutical Science, Yunnan University of Traditional Chinese Medicine, Kunming, China.

Amomi Fructus has been used to treat digestive diseases in the context of traditional Chinese medicine, so we evaluated the effects of a volatile oil from (VOA) on intestinal mucositis induced by 5-fluorouracil (5-FU). We measured the effect of VOA and its main active constituent, bornyl acetate (BA), on body weight, food intake, diarrhea, inflammatory cytokines, the mucosal barrier, and gut microbiota. VOA and BA significantly increased the rats' body weight, relieved diarrhea, and reversed histopathological changes in the gut and inflammation. VOA significantly inhibited apoptosis and alleviated the endoenteritis by downregulating p38 MAPK and caspase-3 expression. VOA and BA strengthened the intestinal mucosal barrier by increasing zonula occludin-1 and occludin expression. VOA and BA reduced the amount of pathogenic bacteria and increased the abundance of probiotics. Thus, VOA prevented the development and progression of intestinal mucositis after chemotherapy.
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http://dx.doi.org/10.3389/fphar.2017.00786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684147PMC
November 2017

MTBP inhibits migration and metastasis of hepatocellular carcinoma.

Clin Exp Metastasis 2015 Apr 11;32(4):301-11. Epub 2015 Mar 11.

Diagnosis and Treatment Center for Liver Cirrhosis, 302 Military Hospital of China, Beijing, 10039, People's Republic of China.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with increasing incidence. Despite curative surgical resection and advanced chemotherapy, its survival rate remains low. The presence of microvascular invasion and occult metastasis is one of the major causes for this poor outcome. MDM2 Binding Protein (MTBP) has been implicated in the suppression of cell migration and cancer metastasis. However, clinical significance of MTBP, particularly in human cancer, is poorly understood. Specifically, clinical relevance of MTBP in human HCC has never been investigated. Here we demonstrated that expression of MTBP was significantly reduced in human HCC tissues compared to adjacent non-tumor tissues. MTBP expression was negatively correlated with capsular/vascular invasion and lymph node metastasis. Overexpression of MTBP resulted in the suppression of the migratory and metastatic potential of HCC cells, while its downregulation increased the migration. Consistent with the previous report, MTBP endogenously bound to alpha-actinin 4 (ACTN4) and suppressed ACTN4-mediated cell migration in multiple HCC cell lines. However, MTBP also inhibited migratory potential of PLC/PRF/5 HCC cells whose migration was not altered by manipulation of ACTN4 expression. These results suggest that mechanisms behind MTBP-mediated migration suppression may not be limited to the pathway involving ACTN4 in certain cellular contexts. Additionally, as a potential mechanism for reduced MTBP expression in tumors, we found that MTBP expression was increased following the treatment with histone deacetylase inhibitors (HDIs). Our study, for the first time, provides clinical relevance of MTBP in the suppression of HCC metastasis.
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http://dx.doi.org/10.1007/s10585-015-9706-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4510982PMC
April 2015

A peptide derived from phage display library exhibits anti-tumor activity by targeting GRP78 in gastric cancer multidrug resistance cells.

Cancer Lett 2013 Oct 20;339(2):247-59. Epub 2013 Jun 20.

State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an 710032, China.

Multidrug resistance (MDR) remains a significant challenge to the clinical treatment of gastric cancer (GC). In the present study, using a phage display approach combined with MTT assays, we screened a specific peptide GMBP1 (Gastric cancer MDR cell-specific binding peptide), ETAPLSTMLSPY, which could bind to the surface of GC MDR cells specifically and reverse their MDR phenotypes. Immunocytochemical staining showed that the potential receptor of GMBP1 was located at the membrane and cytoplasm of MDR cells. In vitro and in vivo drug sensitivity assays, FACS analysis and Western blotting confirmed that GMBP1 was able to re-sensitize MDR cells to chemical drugs. Western blotting and proteomic approaches were used to screen the receptor of GMBP1, and GRP78, a MDR-related protein, was identified as a receptor of GMBP1. This result was further supported by immunofluoresence microscopy and Western blot. Additionally, Western blotting demonstrated that pre-incubation of GMBP1 in MDR cells greatly diminished MDR1, Bcl-2 and GRP78 expression but increased the expression of Bax, whereas downregulation of GRP78, function as a receptor and directly target for GMBP1, only inhibited MDR1 expression. Our findings suggest that GMBP1 could re-sensitize GC MDR cells to a variety of chemotherapeutic agents and this role might be mediated partly through down-regulating GRP78 expression and then inhibiting MDR1 expression. These findings indicate that peptide GMBP1 likely recognizes a novel GRP78 receptor and mediates cellular activities associated with the MDR phenotype, which provides new insight into research on the management of MDR in gastric cancer cells.
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http://dx.doi.org/10.1016/j.canlet.2013.06.016DOI Listing
October 2013

SDR9C7 promotes lymph node metastases in patients with esophageal squamous cell carcinoma.

PLoS One 2013 14;8(1):e52184. Epub 2013 Jan 14.

State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, People's Republic of China.

Background: The major reason for the poor prognosis of esophageal squamous cell carcinoma (ESCC) patients is lymph node (LN) metastases.

Methodology/principal: In the present study, gene expression profiling assay (GEP) was performed to identify the differences in gene expression profiles between primary ESCC tumors that were with LN metastases (N(+)) and those without LN metastases (N(-)).

Conclusions/significance: A total of 23 genes were identified as being significantly elevated, and 30 genes were sharply decreased in ESCC tumors that were N(+) compared with N- tumors. Among these genes, two transcripts of the short chain dehydrogenase/reductase family 9C, member 7 (SDR9C7) were observed 7 times more frequently in N(+) compared with N(-) tumors. Immunohistochemical staining showed that SDR9C7 expression closely correlated with metastasis, and would be a prognostic marker for ESCC patients. To investigate the role of SDR9C7 in the ESCC metastasis, repeated transwell assays were adopted to establish highly and non-invasive ESCC sublines, and western blot showed that SDR9C7 expression was markedly higher in highly invasive cells compared with non-invasive ones. Down-regulation of SDR9C7 dramatically inhibited the metastatic abilities in vitro and in vivo, and repressed the expression of MMP11 in highly invasive cells, indicating that SDR9C7 promotes ESCC metastasis partly through regulation of MMP11, and might be a potential prognostic and therapeutic marker for ESCC patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0052184PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544840PMC
July 2013

MicroRNA-501 promotes HBV replication by targeting HBXIP.

Biochem Biophys Res Commun 2013 Jan 22;430(4):1228-33. Epub 2012 Dec 22.

State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China.

MicroRNAs (miRNAs) can negatively regulate gene expression and also induce or inhibit viral replication. In the present study, we found 10 miRNAs were differentially expressed in a stable HBV-producing cell line (HepG2.2.15) compared with its control cell line (HepG2) by miRNA array analysis. miR-501 was significantly up-regulated in HepG2 cells and tissues with high-HBV replication. miR-501 expression was significantly up-regulated in hepatocellular carcinoma tissues, where HBV replication kept high. Down-regulating miR-501 could significantly inhibit HBV replication, but not influence the growth of HepG2.2.15 cells. Luciferase reporter and western blot assays revealed that HBXIP, an inhibitor of HBV replication, was a potential target of miR-501. Moreover, knockdown of HBXIP rescued the inhibition of HBV that occurred after the loss of miR-501 in HepG2.2.15 cells, suggesting that miR-501 induced HBV replication partially by targeting HBXIP. Thus, knockdown of miR-501 might provide a new mechanism and therapeutic target for inhibiting HBV replication.
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http://dx.doi.org/10.1016/j.bbrc.2012.12.071DOI Listing
January 2013

Positive and negative relationship between anxiety and depression of patients in pain: a bifactor model analysis.

PLoS One 2012 18;7(10):e47577. Epub 2012 Oct 18.

Department of Psychology, Fourth Military Medical University, Xi'an, People's Republic of China.

Background: The relationship between anxiety and depression in pain patients has not been clarified comprehensively. Previous research has identified a common factor in anxiety and depression, which may explain why depression and anxiety are strongly correlated. However, the specific clinical features of anxiety and depression seem to pull in opposite directions.

Objective: The purpose of this study is to develop a statistical model of depression and anxiety, based on data from pain patients using Hospital Anxiety and Depression Scale (HADS). This model should account for the positive correlation between depression and anxiety in terms of a general factor and also demonstrate a latent negative correlation between the specific factors underlying depression and anxiety.

Methods: The anxiety and depression symptoms of pain patients were evaluated using the HADS and the severity of their pain was assessed with the visual analogue scale (VAS). We developed a hierarchical model of the data using an IRT method called bifactor analysis. In addition, we tested this hierarchical model with model fit comparisons with unidimensional, bidimensional, and tridimensional models. The correlations among anxiety, depression, and pain severity were compared, based on both the bidimensional model and our hierarchical model.

Results: The bidimensional model analysis found that there was a large positive correlation between anxiety and depression (r = 0.638), and both scores were significantly positively correlated with pain severity. After extracting general factor of distress using bifactor analysis, the specific factors underlying anxiety and depression were weakly but significantly negatively correlated (r = -0.245) and only the general factor was significantly correlated with pain severity. Compared with the three first-order models, the bifactor hierarchical model had the best model fit.

Conclusion: Our results support the hypothesis that apart from distress, anxiety and depression are inversely correlated. This finding has not been convincingly demonstrated in previous research.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0047577PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475698PMC
April 2013

Ectopic expression of MiR-125a inhibits the proliferation and metastasis of hepatocellular carcinoma by targeting MMP11 and VEGF.

PLoS One 2012 29;7(6):e40169. Epub 2012 Jun 29.

State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, PR China.

Background: Studies have been shown that miR-125a plays an important role in carcinogenesis, however, the role of miR-125a in hepatocellular carcinoma (HCC) remains elusive.

Methodology/principal: Real time-PCR (qRT-PCR) was performed to test the significance of miR-125a in HCC. Ectopic expression of miR-125a was used to test the influences of miR-125a on proliferation and metastasis of HCC cells in vitro and in vivo. Predicted target genes of miR-125a were determined by dual-luciferase reporting, qRT-PCR, and western blot (WB) analyses. Then immunohistochemical staining (IHC) was used to detect the expression of target genes, and the correlations and prognostic values of miR-125a and its target genes were also investigated.

Conclusions/significance: Decreased miR-125a was observed in both HCC tissues and cell lines, and associated with patients' aggressive pathologic features. Up-regulating miR-125a significantly inhibited the malignant phenotypes by repressing the expression of matrix metalloproteinase 11 (MMP11) and vascular endothelial growth factor A (VEGF-A) both in vitro and in vivo. Furthermore, miR-125a expression was inversely correlated with both MMP11 and VEGF-A expression in HCC tissues. Inhibiting miR-125a could increase both MMP11 and VEGF-A expression, and RNA interference targeting MMP11 or VEGF-A mRNA could rescue the loss of miR-125a functions. MiR-125a inhibits the proliferation and metastasis of HCC by targeting MMP11 and VEGF-A. Up-regulation of miR-125a might be a promising approach and a prognostic marker for HCC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0040169PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387011PMC
November 2012

PCP can enhance dendritic cells to present the HBsAg peptide.

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2011 Feb;27(2):215-9

State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.

Aim: To investigate the influence of paraclorophenol (pCP) on dendritic cells loading and presenting HBsAg from peripheral blood monocytes of healthy volunteers identified as hepatitis B vaccine nonresponders.

Methods: The density gradient centrifugation was performed to isolate mononuclear cells from 10 hepatitis B vaccine nonresponders. The adherent monocytes were incubated with HBsAg adding rhGM-CSF and rhIL-4 in the presence of absence of pCP for 7 days. Then the supernatant was collected for ELISA assays. The culture medium system without pCP was used as negative control and without pCP or HBsAG was named blank control. the matured DCs were co-incubated with autologous T lymphocytes for 72h and the supernatant was also collected for ELISA assays.

Results: In the presence of pCP, the level of IL-12 in supernate (265.68± 16.21) ng/L was significantly higher than the negative control (168.76±10.01) ng/L (P<0.05) and blank control (87±5.79)ng/L (P<0.05); after co-incubated with autologous T lymphocytes for 3 days, the level of IFN-γ with pCP (773.04±32.73) mg/L was also significantly higher than the negative control (573.59±26.11) mg/L (P<0.05) ans blank control (362.81±24.27)mg/L (P<0.05).

Conclusion: pCP can effectively enhance the dendritic cells loading and presenting HBsAg from peripheral blood monocytes of healthy volunteers identified as hepatitis B vaccine nonresponders, which also can dramatically increase te autologous T lymphocytes response.7
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February 2011

Gankyrin promotes the proliferation of human pancreatic cancer.

Cancer Lett 2010 Nov 18;297(1):9-17. Epub 2010 May 18.

Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, China.

Previous studies in our laboratory have suggested that gankyrin expression is correlated with a malignant phenotype in colorectal cancer. Here, we investigated the possible role of gankyrin in pancreatic carcinogenesis. Gankyrin expression was significantly increased in pancreatic cancer compared to non-cancerous tissues. This expression significantly enhanced cancer cell proliferation and growth in vitro and in vivo. Suppression of gankyrin downregulated cyclin A, cyclin D1, cyclin E, CDK2, CDK4, PCNA and p-Rb but upregulated p27, Rb and p53. However, gankyrin overexpression led to opposite results. Thus, gankyrin could enhance pancreatic cancer cell proliferation by promoting cell cycle progression and p53 degradation.
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http://dx.doi.org/10.1016/j.canlet.2010.04.019DOI Listing
November 2010

Overexpression of a novel gene gankyrin correlates with the malignant phenotype of colorectal cancer.

Cancer Biol Ther 2010 Jan 9;9(2):88-95. Epub 2010 Jan 9.

State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi Province, China.

Gankyrin, a small and highly conserved protein which is identical to the p28 gene product, was found to be related with the malignant phenotypes in liver and esophageal carcinoma. However, the roles of gankyrin in colorectal carcinoma (CRC) are still unknown. In the present study, the gankyrin mRNA and protein expression in human CRC cell lines and clinical tissue samples were evaluated and correlated with clinicopathological features. Possible mechanisms by which gankyrin regulates the malignant phenotype of CRC cells were also investigated. The results demonstrated that gankyrin was obviously overexpressed in CRC tissues and cell lines compared to controls, and gankyrin expression was correlated with TNM stages and metastasis of CRC. Overexpression of gankyrin by PhkitNeo-hGankyrin plasmid transfected into Lovo cells could promote the cell proliferation and tumorigenicity. This finding was further strengthened by experiments that suppressing gankyrin expression by siRNA exerted the opposite effects on CRC cells SW620. In addition, our present study showed that the co-expression of cyclinD1 and beta-catenin were positive correlation with the alteration of gankyrin expression. This data suggested that gankyrin played significant roles in the pathogenesis of human CRC, and might be an important therapeutic target for CRC.
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http://dx.doi.org/10.4161/cbt.9.2.10283DOI Listing
January 2010

URG11 mediates hypoxia-induced epithelial-to-mesenchymal transition by modulation of E-cadherin and beta-catenin.

Biochem Biophys Res Commun 2010 Jan 11;391(1):135-41. Epub 2009 Nov 11.

Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an, PR China.

Upregulated gene 11 (URG11), recently identified as a new HBx-upregulated gene that may activate beta-catenin and Wnt signaling, was found to be upregulated in a human tubule cell line under low oxygen. Here, we investigated the potential role of URG11 in hypoxia-induced renal tubular epithelial-to-mesenchymal (EMT). Overexpression of URG11 in a human proximal tubule cell line (HK2) promoted a mesenchymal phenotype accompanied by reduced expression of the epithelial marker E-cadherin and increased expression of the mesenchymal markers vimentin and alpha-SMA, while URG11 knockdown by siRNA effectively reversed hypoxia-induced EMT. URG11 promoted the expression of beta-catenin and increased its nuclear accumulation under normoxic conditions through transactivation of the beta-catenin promoter. This in turn upregulated beta-catenin/T-cell factor (TCF) and its downstream effector genes, vimentin, and alpha-SMA. In vivo, strong expression of URG11 was observed in the tubular epithelia of 5/6-nephrectomized rats, and a Western blot analysis demonstrated a close correlation between HIF-1alpha and URG11 protein levels. Altogether, our results indicate that URG11 mediates hypoxia-induced EMT through the suppression of E-cadherin and the activation of the beta-catenin/TCF pathway.
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http://dx.doi.org/10.1016/j.bbrc.2009.11.019DOI Listing
January 2010
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