No abstract available.
Up-Regulation*

p11 protein (S100A10) is downregulated in depressive-like states of human and rodent. Antidepressant drug treatment increases p11 levels in rodent models. We reviewed studies demonstrating that p11 levels are regulated in depression and by antidepressant treatment and that p11 upregulation exerts antidepressant effects. Current studies on p11 underscore the importance of p11 as a potential antidepressant target.
Depression* ; Humans ; Rodentia ; Up-Regulation

No abstract available.
Animals ; Hyperalgesia ; Microglia ; Rats ; Up-Regulation

OBJECTIVETo investigate the whole genome expression profiles between gastric high-grade intraepithelial neoplasia (HGIN) tissues with cancer and HGIN tissues without cancer.

METHODSGastric specimens from an upper magnifying chromoendoscopic targeted biopsy were collected at Peking Union Medical College Hospital from March 2010 to May 2013. Each of the forceps biopsies from the 21 patients was HGIN,but there were 10 HGIN and 11 HGIN with cancer after the endoscopic submucosal dissection. The whole genome expression profiling was performed on 10 HGIN samples and 11 HGIN with cancer samples using Agilent 4 × 44K Whole Human Genome microarrays. Differentially expressed genes between different types of lesions were identified using an unpaired t-test and corrected with the Benjamini and Hochberg false discovery rate algorithm. A gene ontology(GO)enrichment analysis was performed using the GeneSpring software GX 12.6.

RESULTSThe gene expression patterns were different between HGIN tissues with cancer and HGIN tissues without cancer. There were 470 significantly differentially expressed transcripts between them (P<0.05,Fold Change>2), with 180 up-regulated genes and 290 down-regulated genes in HGIN tissues with cancer. A GO enrichment analysis demonstrated that the most striking over-expressed transcripts in HGIN with cancer were in the category of triglyceride biosynthetic process,acylglycerol biosynthetic process,neutral lipid biosynthetic process,glycerol ether metabolic process,organic ether metabolic process,and glycerolipid metabolic process.

CONCLUSIONThe change of lipid metabolism may contribute to the pathogenesis of gastric cancer at an early stage.

Algorithms ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; Genome, Human ; Humans ; Lipid Metabolism ; Software ; Stomach Diseases ; Stomach Neoplasms ; Up-Regulation

OBJECTIVETo examine the micro-RNA (mirna) expression profile in tissues of early gastric cancer and to screen the specific mirna associated with gastric cancer.

METHODSGene chip technology was used to detect the expression of mirna in early gastric cancer tissues and adjacent normal tissues.

RESULTSCompared to adjacent normal tissues, a total of 36 mirnas were down-regulated, such as mir-9-1, mir-103 and mir-141, while 12 mirnas were up-regulated, such as mir-196a, mir-142-3p and mir-25, etc.

CONCLUSIONAbnormal mirna expression level in early gastric cancer tissues may be associated to the development of gastric cancer.

Down-Regulation ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs ; genetics ; Oligonucleotide Array Sequence Analysis ; Stomach Neoplasms ; genetics ; Up-Regulation

Osteocytes may function as mechanotransducers by regulating local osteoclastogenesis. Reduced availability of oxygen, i.e. hypoxia, could occur during disuse, bone development, and fracture. Receptor activator of nuclear factor-kappaB ligand (RANKL) is an osteoblast/stromal cell derived essential factor for osteoclastogenesis. The hypoxia induced osteoclastogenesis via increased RANKL expression in osteoblasts was demonstrated. Hypoxic regulation of gene expression generally involves activation of the hypoxia-inducible factor (HIF) transcription pathway. In the present study, we investigated whether hypoxia regulates RANKL expression in murine osteocytes and HIF-1alpha mediates hypoxia-induced RANKL expression by transactivating RANKL promoter, to elucidate the role of osteocyte in osteoclastogenesis in the context of hypoxic condition. The expression levels of RANKL mRNA and protein, as well as hypoxia inducible factor-1alpha (HIF-1alpha) protein, were significantly increased in hypoxic condition in MLO-Y4s. Constitutively active HIF-1alpha alone significantly increased the levels of RANKL expression in MLO-Y4s under normoxic conditions, whereas dominant negative HIF-1alpha blocked hypoxia-induced RANKL expression. To further explore to find if HIF-1alpha directly regulates RANKL transcription, a luciferase reporter assay was conducted. Hypoxia significantly increased RANKL promoter activity, whereas mutations of putative HIF-1alpha binding elements in RANKL promoter prevented this hypoxia-induced RANKL promoter activity in MLO-Y4s. These results suggest that HIF-1alpha mediates hypoxia-induced up-regulation of RANKL expression, and that in osteocytes of mechanically unloaded bone, hypoxia enhances osteoclastogenesis, at least in part, via an increased RANKL expression in osteocytes.
Anoxia* ; Bone Development ; Gene Expression Regulation ; Luciferases ; Osteoblasts ; Osteocytes* ; Oxygen ; RANK Ligand* ; RNA, Messenger ; Up-Regulation

BACKGROUND: UVB irradiation induces apoptosis or/and autophagy through several molecular pathways in keratinocytes. However, the precise molecular mechanism of UVB-induced autophagy is largely unknown in keratinocytes. OBJECTIVE: The purpose of this study was to investigate the molecular mechanisms of UVB-induced apoptosis and autophagy in HaCaT cell lines. METHODS: Cells were irradiated by UVB (Westinghouse FS-40 sunlamps) with various doses (0, 30, 60, 120, 240 mJ/cm2). The expression levels of caspase-3, Bax, Bcl2, Bcl-X(L) and LC3 were confirmed by Western blot analysis in UVB-irradiated HaCaT cell lines. Apoptotic cells were analyzed by PI staining, and autophagy cells were analyzed by immunofluorescent staining. RESULTS: The expression of Bcl-X(L) decreased from UVB 60 mJ/cm2 and Bcl2 decreased from UVB 240 mJ/cm2. The expression of caspase-3 was increased from UVB 120 mJ/cm2. These data showed that UVB-induced apoptosis is mediated by up-regulation of caspase-3 and down-regulation of Bcl2 and Bcl-X(L). Furthermore, the expression of LC3 increased from UVB 120 mJ/cm2. In addition, autophagy formation was observed in few fractions of apoptotic HaCaT cells in immunofluorescent staining; most apoptotic cells did not show autophagy formation. Moreover, autophagy formation inhibitor treatment induced a slight increment of apoptotic cell population under UVB irradiation. CONCLUSION: UVB irradiation induces not only apoptotic cell death but also autophagy formations; these events may create a defense mechanism for the prevention of apoptosis in UVB-treated HaCaT cells.
Apoptosis ; Autophagy ; Blotting, Western ; Caspase 3 ; Cell Death ; Cell Line ; Down-Regulation ; Keratinocytes ; Up-Regulation

PURPOSE: The purpose of this study is to analyze the mechanism of RECK gene (a novel MMP inhibitor) in human osteosarcoma and evaluation of RECK as a prognostic factor and therapeutic target. MATERIALS AND METHODS: Osteosarcoma cell lines were established from tumor samples of 23 patients who had been treated from March 2003 to April 2004 and 4 standard cell lines (HOS, MG-63, SaOS-2, U-2OS). We isolated the RNA from 27 cell lines and evaluated the expression level of RECK gene using quantitative real time-PCR method. MMP-2 and MMP-9 expression were evaluated by gelatin zymography. Five cell lines were selected which had a statistical significance between RECK gene up-regulation and MMP expression (p=0.01). Then 5 cell lines and 3 standard cell lines were transfected by RECK gene. We compared RECK gene expression with MMP down-regulation between transfected cell lines and non-transfected cell lines. Invasion of transfected cell lines were evaluated by invasion assay using matrigel. RESULTS: RECK genes were expressed in all cell lines and 1 cell line showed especially high expression. In zymography, pro-MMP-2 was expressed in almost cell lines whereas pro-MMP-9 was rarely expressed. RECK gene expressions were increasingly high and MMP expressions were low in transfected cell lines via zymography. Transfected HOS cells decreased invasiveness in matrigel invasion assay and showed small number of migrated cells. It had a statistical significance (p<0.01). CONCLUSION: It is expected that down-regulation of MMP by RECK gene expression can be used as a biologic marker. It can be a new therapeutic strategies and valuable prognostic factors in treating osteosarcoma.
Biomarkers ; Cell Line ; Down-Regulation ; Gelatin ; Gene Expression ; Humans ; Osteosarcoma* ; RNA ; Transfection ; Up-Regulation

OBJECTIVETo investigate the regulatory effects of miR-18a on chemotherapeutic sensitivity of leukemia cell HL-60 to VP-16 and VCR, and explore its molecular mechamism.

METHODSThe HL-60 PC DNA3.1-miR-18A cell line with stably overexpressing miR-18a was constructed and their sensitivity to VP-16 and VCR was detected. The luciferase reporter vector of ATM 3'UTR region was constructed and the targeting effect of miR-18a on ATM was identified. The expression level of ATM in HL-60 cells overexpressing miR-18a was detected by Western blot. The seusitivity of HL-60 cells with knockdown of ATM to VP-16 and VCR was detected by CCK-8 method. The ATM expression level in HL-60 cells with stably overexpression miR-18a after transfection of miR-18a inhibitor was detected by using Western blot and the sensitivity changes of these HL-60 cells to VP-16 and BCR were detected.

RESULTSAfter overexpression of miR-18a, the viability of HL-60 cells treated with VP-16 and VCR of same concentration decreased; the detectiion of luciferase activity showed that the miR-18a could inhitit activity of luciferase reporter vector of ATM; the expression level of ATM in HL-60 cells was down-regulated after transfection with miR-18a; the cell viability decreased when HL-60 cells were treated with VP-16 and VCR after knockdown of ATM; the expression level of ATM was up-regulated and the cell viability decreased when HL-60 cells were treated with VP-16 and VCR after transfection with miR-18a inhibitor.

CONCLUSIONThe miR-18a can regulated the sensitivity of leukemia HL-60 cells to VP-16 and VCR by targeting ATM.

Antineoplastic Agents ; Down-Regulation ; HL-60 Cells ; Humans ; Leukemia, Promyelocytic, Acute ; MicroRNAs ; Transfection ; Up-Regulation

OBJECTIVETo detect and analyze the characteristic miRNAs profile of anal fistula and explore their possible target genes and potential clinical significance.

METHODSThe anal mucosa close to the hemorrhoids were collected from three patients undergoing fistulectomy and hemorrhoidectomy (fistula group) as well as three patients receiving only hemorroidectomy(hemorrhoids group), matching with fistula group in age, gender and body weight. miRNA microarray was used to compare the expression of 1 285 human miRNAs of the anal mucosa between two groups. Cluster analysis was adopted to analyze the accumulation of the differentially expressed miRNAs(P<0.05, fold≥2.0 or ≤0.5) and their target genes were predicted with 10 softwares such as DIANAmT, miRanda, miRDB, miRWalk etc. Comprehensive scoring was performed to identify genes with highest predictive score. Gene ontology (GO) concentration technique was used to analyze the target gene-associated biological process. Immunohistochemistry was used to examine protein expression of genes with the highest score.

RESULTSAmong 1285 miRNAs in fistula group, 13 miRNAs were differentially expressed with those in hemorrhoid group, including 2 of up-regulation and 11 of down-regulation. Paired t test showed that in fistula group, miRNA-3609 up-regulation was 5.98 folds(P=0.0231) and miR-181a-2-3p down-regulation was 0.13 folds(P=0.0067) compared to those in hemorrhoid group, which had the greatest differential expression. Cluster analysis suggested that up-regulated miR-3609 and miR-6086 had similar change trend in both groups. Among 11 down-regulated miRNAs, miR-125bp-1-3p and miR-548q had similar expression and other 9 miRNAs had similar expression as well, including miR-1185-1-3p, miR-532-3p, miR-1233-5p, miR-769-5p, miR-149-5p, miR-99b-3p, miR-141-3p, miR-138-5p, and miR-181a-2-3p. Target gene prediction analysis of above 13 genes showed that 7 miRNAs(53.8%) were eligible to predict their potential target genes, yielding totally 104 possible target genes. The rest of 6 miRNAs(46.2%) failed to predict any target gene. The highest score in prediction of target gene was chitinase 1(ChIT1) and its corresponding differential miRNA was miR-769-5p(r=-0.94286, P=0.0167). Gene ontology analysis showed that the most associated biological process related with these 104 target genes was keratinization, immune response and signal transduction. Immunohistochemistry revealed ChiT1 expression of anal mucosa in fistula group was significantly higher compared to hemorrhoid group(P<0.01).

CONCLUSIONSThere is a characteristic miRNAs profile in anal fistula patients, which may play a role in the occurrence and development of anal fistula.

Cluster Analysis ; Down-Regulation ; Humans ; MicroRNAs ; Rectal Fistula ; genetics ; Signal Transduction ; Up-Regulation