DNA Hypomethylation-Mediated Overexpression of Carbonic Anhydrase 9 Induces an Aggressive Phenotype in Ovarian Cancer Cells

안정혁,성혜윤,주웅 연세대학교의과대학 2014 Yonsei medical journal Vol.55 No.6

Purpose: Both genetic and epigenetic alterations can lead to abnormal expressionof metastasis-regulating genes in tumor cells. Recent studies suggest that aberrantepigenetic alterations, followed by differential gene expression, leads to an aggressive cancer cell phenotype. We examined epigenetically regulated genes that are involved in ovarian cancer metastasis. Materials and Methods: We developedSK-OV-3 human ovarian carcinoma cell xenografts in mice. We comparedthe mRNA expression and DNA methylation profiles of metastatic tissues to those of the original SK-OV-3 cell line. Results: Metastatic implants showed increased mRNA expression of the carbonic anhydrase 9 (CA9) gene and hypomethylationat CpG sites in the CA9 promoter. Treatment of wild-type SK-OV-3 cells with the DNA methyltransferase inhibitor 5-aza-2’-deoxycytidine reduced methylation of the CA9 promoter and increased CA9 mRNA expression. Eight CpGs, which were located at positions -197, -74, -19, -6, +4, +13, +40, and +86, relative to the transcription start site, were hypomethylated in metastatic tumor implants, compared to that of wild-type SK-OV-3. Overexpression of CA9 inducedan aggressive phenotype, including increased invasiveness and migration, in SK-OV-3 cells. Conclusion: Alterations in the DNA methylation profile of the CA9 promoter were correlated with a more aggressive phenotype in ovarian cancercells.

중소형 이동통신 중계기용 함체의 방열설계

안정혁,송명호 동국대학교 산업기술연구원 2000 산업기술논문집 Vol.11 No.1

Thermal design for medium and small size outdoor enclosures of electronic equipments serving as base stations and repeaters for mobile communication is required in order to prevent the malfunctioning resulting from the excessive temperature rise due to the excessive internal heat generation. Electronic equipments for the repeaters have become smaller in size while they consume gradually more power. In general, outdoor enclosures are mechanically sealed to provide the protection from the dust and moisture contained in the surrounding atmosphere and from the pilferage, which add the difficulties in the release of the internally generated heat. A thermal design for a small size enclosure (300W power consumption) has been completed and the application for the registration is submitted. As the small enclosure has no moving part in order to guarantee the extended life time, it can only utilize extended surface area (fins) and exterior natural convection hear transfer. The optimized configurations of the external fins has the pitch of 8 mm and the thickness of 0.8mm. Since the fin arrays could not be manufactured by the extrusion process, the parallel grooves were carved into the base plate and thin Aluminium plates of nonuniform heights were compression fitted along the grooves. A thermal design for the medium size enclosure (1.1 kW power consumption) design has also been developed and acquired the copy right in registered designs. the medium size enclosure uses heat exchangers and flow driving fans. the constant temperature test booth of 1.5 m and 2 m in length and width, 2.5 m in height has been built and imposed the extreme summer temperature conditions.

Enhancing Performance of Organic Photovoltaics by Energy Transfer with Customized Energy Donor

안정혁,김현탁,권태혁 한국고분자학회 2014 한국고분자학회 학술대회 연구논문 초록집 Vol.2014 No.10

시뮬레이션을 이용한 창호의 결로 판정에 관한 연구

안정혁(Jung-hyuk Ahn),조수(Soo Cho),장문석(Mun-Suck Jang),이풍현(Hyun-Pung Lee) 대한설비공학회 2002 대한설비공학회 학술발표대회논문집 Vol.2002 No.-

Overexpression of Mucin 13 due to Promoter Methylation Promotes Aggressive Behavior in Ovarian Cancer Cells

성혜윤,안정혁,박애경,주웅 연세대학교의과대학 2014 Yonsei medical journal Vol.55 No.5

Purpose: Recent discoveries suggest that aberrant DNA methylation provides cancercells with advanced metastatic properties. However, the precise regulatory mechanismscontrolling metastasis genes and their role in metastatic transformation are largely unknown. To address epigenetically-regulated gene products involved in ovarian cancer metastasis, we examined the mechanisms regulating mucin 13 (MUC13) expression and its influence on aggressive behaviors of ovarian malignancies. Materials and Methods: We injected SK-OV-3 ovarian cancer cells peritoneallyinto nude mice to mimic human ovarian tumor metastasis. Overexpression of MUC13 mRNA was detected in metastatic implants from the xenografts by expressionmicroarray analysis and quantitative reverse-transcription polymerase chain reaction(qRT-PCR). The DNA methylation status within the MUC13 promoter region was determined using bisulfite sequencing PCR and quantitative methylation-specificPCR. We evaluated the effects of exogenous MUC13 on cell invasion and migrationusing in vitro transwell assays. Results: MUC13 mRNA expression was up-regulated,and methylation of specific CpG sites within the promoter was reduced in the metastatic implants relative to those in wild-type SK-OV-3 cells. Addition of a DNA methyltransferase inhibitor to SK-OV-3 cells induced MUC13 expression, thereby implying epigenetic regulation of MUC13 by promoter methylation. MUC13 overexpressionincreased migration and invasiveness, compared to control cells, suggestingaberrant up-regulation of MUC13 is strongly associated with progression of aggressivebehaviors in ovarian cancer. Conclusion: We provide novel evidence for epigenetic regulation of MUC13 in ovarian cancer. We suggest that the DNA methylationstatus within the MUC13 promoter region may be a potential biomarker of aggressive behavior in ovarian cancer.

Aberrant Hypomethylation of Solute Carrier Family 6 Member 12 Promoter Induces Metastasis of Ovarian Cancer

성혜윤,안정혁,양산덕,박애경,주웅 연세대학교의과대학 2017 Yonsei medical journal Vol.58 No.1

Purpose: Ovarian cancer (OC) is the most fatal of gynecological malignancies with a high rate of recurrence. We aimed to evaluatethe expression of solute carrier family 6, member 12 (SLC6A12) and methylation of its promoter CpG sites in a xenograft mousemodel of metastatic OC, and to investigate the regulatory mechanisms that promote aggressive properties during OC progression. Materials and Methods: Expression of SLC6A12 mRNA was determined by reverse-transcription quantitative polymerase chainreaction (RT-qPCR), and DNA methylation status of its promoter CpGs was detected by quantitative methylation-specific PCR. Themetastatic potential of SLC6A12 was evaluated by in vitro migration/invasion transwell assays. Gene expression and DNA methylationof SLC6A12 and clinical outcomes were further investigated from publicly available databases from curatedOvarianDataand The Cancer Genome Atlas. Results: SLC6A12 expression was 8.1–14.0-fold upregulated and its DNA methylation of promoter CpG sites was 41–62% decreasedin tumor metastases. After treatment with DNA methyltransferase inhibitor and/or histone deacetylase inhibitor, the expression ofSLC6A12 was profoundly enhanced (~8.0-fold), strongly supporting DNA methylation-dependent epigenetic regulation of SLC6A12. Overexpression of SLC6A12 led to increased migration and invasion of ovarian carcinoma cells in vitro, approximately 2.0-fold and3.3-fold, respectively. The meta-analysis showed that high expression of SLC6A12 was significantly associated with poor overall survival[hazard ratio (HR)=1.07, p value=0.016] and that low DNA methylation levels of SLC6A12 at specific promoter CpG site negativelyaffected patient survival. Conclusion: Our findings provide novel evidence for the biological and clinical significance of SLC6A12 as a metastasis-promotinggene.

Effect of Necrosis on the miRNA-mRNA Regulatory Network in CRT-MG Human Astroglioma Cells

안소희,안정혁,류동열,이지수,조민선,최윤희 대한암학회 2018 Cancer Research and Treatment Vol.50 No.2

Purpose Glioblastoma multiforme (GBM) is the most common adult primary intracranial tumor. The remarkable features of GBM include central necrosis. MicroRNAs (miRNAs) have been considered as diagnostic/prognostic biomarkers for many cancers, including glioblastoma. However, the effect of necrosis on the miRNA expression profile and predicted miRNA-mRNA regulatory information remain unclear. The purpose of this study is to examine the effect of necrotic cells on the modulation of miRNA and mRNA expression profiles and miRNA-mRNA network in CRT-MG cells. Materials and Methods We used human astroglioma cells, CRT-MG, treated with necrotic CRT-MG cells to examine the effect of necrosis on the modulation of miRNA and mRNA by next-generation sequencing. For preparation of necrotic cells, CRT-MG cells were frozen and thawed through cycle of liquid nitrogen–water bath. The putative miRNA-mRNA regulatory relationship was inferred through target information, using miRDB. Results The necrotic cells induced dysregulation of 106 miRNAs and 887 mRNAs. Among them, 11 miRNAs that had a negative correlation value of p < 0.05 by the hypergeometric test were screened, and their target mRNAs were analyzed by Gene Ontology enrichment analysis. Using the Kyoto Encyclopedia of Genes and Genomes database, we also found several necrotic cell treatment-activated pathways that were modulated by relevant gene targets of differentially expressed miRNAs. Conclusion Our result demonstrated that dysregulation of miRNA and mRNA expression profiles occurs when GBM cells are exposed to necrotic cells, suggesting that several miRNAs may have the potential to be used as biomarkers for predicting GBM progression and pathogenesis.

알루미늄 薄膜과 合成樹脂 多隔室 構造로 이루어진 板形 素材의 斷熱 特性

이온구,이동진,안정혁,송명호 동국대학교 산업기술환경대학원 1998 산업기술논총 Vol.4 No.-

An experimental and theoretical study on heat transfer characteristics of a polymer bubble film sandwiched between two aluminium foils has been conducted in order to obtain better understanding required for improved design of reflective insulation materials. Mathematical models, accounting for diffusive, convective and radiative mode of energy transfer and utilizing equivalent thermal resistance circuit, were set up. The predicted value of effective heat transfer coefficient served as reference for the measured effective thermal conductivities. The effective thermal conductivities of the specimen were also experimentally determined from the measured values of temperature difference and heat generation rate utilizing guarded hot box method for different orientations of specimen relative to the gravity direction and for different temperatures. The predicted and measured results showed good agreements and revealed that insulation decreases as the temperature difference increases when the imposed temperature gradient is either horizontal or downward. The smaller bubble size then those of present specimen is desirable for better insulation performance.

Regulatory B Subunits of Protein Phosphatase 2A Are Involved in Site-specific Regulation of Tau Protein Phosphorylation

유은영,유병철,안정혁 대한약리학회 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.2

Overexpression of amyloid precursor protein with the Swedish mutation causes abnormal hyperphosphorylationof the microtubule-associated protein tau. Hyperphosphorylated isoforms of tau are majorcomponents of neurofibrillary tangles, which are histopathological hallmarks of Alzheimer’s disease. Protein phosphatase 2A (PP2A), a major tau protein phosphatase, consists of a structural A subunit,catalytic C subunit, and a variety of regulatory B subunits. The B subunits have been reported tomodulate function of the PP2A holoenzyme by regulating substrate binding, enzyme activity, andsubcellular localization. In the current study, we characterized regulatory B subunit-specific regulationof tau protein phosphorylation. We showed that the PP2A B subunit PPP2R2A mediated dephosphorylationof tau protein at Ser-199, Ser-202/Thr-205, Thr-231, Ser-262, and Ser-422. Down-regulation ofPPP2R5D expression decreased tau phosphorylation at Ser-202/Thr-205, Thr-231, and Ser-422, whichindicates activation of the tau kinase glycogen synthase kinase 3 beta (GSK3β ) by PP2A withPPP2R5D subunit. The level of activating phosphorylation of the GSK3β kinase Akt at Thr-308 andSer-473 were both increased by PPP2R5D knockdown. We also characterized B subunit-specific phosphorylationsites in tau using mass spectrometric analysis. Liquid chromatography-mass spectrometryrevealed that the phosphorylation status of the tau protein may be affected by PP2A, depending onthe specific B subunits. These studies further our understanding of the function of various B subunitsin mediating site-specific regulation of tau protein phosphorylation.

하인두암에서 선행항암화학요법 후 방사선치료의 의의

왕수건,이병주,고의경,김태원,안정혁,정주섭,김동원,남지호 대한이비인후과학회 2003 대한이비인후과학회지 두경부외과학 Vol.46 No.12

Background and Objectives:Hypopharyngeal cancer is notorious for its poor prognosis and severe surgical morbidity with functional deficits. This study was conducted to compare the efficacy between the neoadjuvant chemotherapy followed by radio-therapy and surgery with postoperative radiotherapy in the treatment of hypophayngeal cancer. Material and Method:Medical records of 64 patients, treated for hypopharyneal cancer at Pusan National University Hospital from March 1986 through May 2000, were retrospectively reviewed. Thirty-three patients were grouped into the chemotherapy and radiotherapy (CRTx) group, who received neoadjuvant chemotherapy and radiotherapy. Thirty-one patients were grouped into the operation and radiotherapy (ORTx) group, who received laryngectomy with or without reconstruction and postoperative radiotherapy. Results:There was no significant difference of thre years survival rate between CRTx group and ORTx group (p>0.05). Laryngeal preservation rate was 45% in CRTx group but 3% in ORTx group (p<0.05). Conclusion:Although this had not been a randomized study of chemotherapy followed by radiotherapy versus surgery plus postoperative radiotherapy, the survival rate of CRTx group appears to be as identical as ORTx group and more effective in the preservation of the larynx. (Korean J Otolaryngol 2003 ;46 :1058-63)