Gα₁₂ gep oncogene deregulation of p53-responsive microRNAs promotes epithelial–mesenchymal transition of hepatocellular carcinoma

Yang, Y M,Lee, W H,Lee, C G,An, J,Kim, E-S,Kim, S H,Lee, S-K,Lee, C H,Dhanasekaran, D N,Moon, A,Hwang, S,Lee, S J,Park, J-W,Kim, K M,Kim, S G Macmillan Publishers Limited 2015 Oncogene Vol.34 No.22

Hepatocellular carcinoma (HCC) has a poor prognosis owing to aggressive phenotype. Gα<SUB>12</SUB> gep oncogene product couples to G-protein-coupled receptors, whose ligand levels are frequently increased in tumor microenvironments. Here, we report Gα<SUB>12</SUB> overexpression in human HCC and the resultant induction of zinc-finger E-box-binding homeobox 1 (ZEB1) as mediated by microRNA deregulation. Gα<SUB>12</SUB> expression was higher in HCC than surrounding non-tumorous tissue. Transfection of Huh7 cell with an activated mutant of Gα<SUB>12</SUB> (Gα<SUB>12</SUB>QL) deregulated microRNA (miRNA or miR)-200b/a/429, -194-2/192 and -194-1/215 clusters in the miRNome. cDNA microarray analyses disclosed the targets affected by Gα<SUB>12</SUB> gene knockout. An integrative network of miRNAs and mRNA changes enabled us to predict ZEB1 as a key molecule governed by Gα<SUB>12</SUB>. Decreases of miR-200a/b, -192 and -215 by Gα<SUB>12</SUB> caused ZEB1 induction. The ability of Gα<SUB>12</SUB> to decrease p53 levels, as a result of activating protein-1 (AP-1)/c-Jun-mediated mouse double minute 2 homolog induction, contributed to transcriptional deregulation of the miRNAs. Gα<SUB>12</SUB>QL induced ZEB1 and other epithelial–mesenchymal transition markers with fibroblastoid phenotype change. Consistently, transfection with miR-200b, -192 or -215 mimic prevented the ability of Gα<SUB>12</SUB>QL to increase tumor cell migration/invasion. In xenograft studies, sustained knockdown of Gα<SUB>12</SUB> decreased the overall growth rate and average volume of tumors derived from SK-Hep1 cell (mesenchymal-typed). In HCC patients, miR-192, -215 and/or -200a were deregulated with microvascular invasion or growth advantage. In the HCC samples with higher Gα<SUB>12</SUB> level, a correlation existed in the comparison of relative changes of Gα<SUB>12</SUB> and ZEB1. In conclusion, Gα<SUB>12</SUB> overexpressed in HCC causes ZEB1 induction by deregulating p53-responsive miRNAs, which may facilitate epithelial–mesenchymal transition and growth of liver tumor. These findings highlight the significance of Gα<SUB>12</SUB> upregulation in liver tumor progression, implicating Gα<SUB>12</SUB> as an attractive therapeutic target.

The gep oncogenes, Gα₁₂ and Gα₁₃, upregulate the transforming growth factor-β1 gene

Lee, S J,Yang, J W,Cho, I J,Kim, W D,Cho, M K,Lee, C H,Kim, S G Macmillan Publishers Limited 2009 Oncogene Vol.28 No.9

Transforming growth factor-β1 (TGFβ1) plays a role in neoplastic transformation and transdifferentiation. Gα<SUB>12</SUB> and Gα<SUB>13</SUB>, referred to as the gep oncogenes, stimulate mitogenic pathways. Nonetheless, no information is available regarding their roles in the regulation of the TGFβ1 gene and the molecules linking them to gene transcription. Knockdown or knockout experiments using murine embryonic fibroblasts and hepatic stellate cells indicated that a Gα<SUB>12</SUB> and Gα<SUB>13</SUB> deficiency reduced constitutive, auto-stimulatory or thrombin-inducible TGFβ1 gene expression. In contrast, transfection of activated mutants of Gα<SUB>12</SUB> and Gα<SUB>13</SUB> enabled the knockout cells to promote TGFβ1 induction. A promoter deletion analysis suggested that activating protein 1 (AP-1) plays a role in TGFβ1 gene transactivation, which was corroborated by the observation that a deficiency of the G-proteins decreased the AP-1 activity, whereas their activation enhanced it. Moreover, mutation of the AP-1-binding site abrogated the ability of Gα<SUB>12</SUB> and Gα<SUB>13</SUB> to induce the TGFβ1 gene. Transfection of a dominant-negative mutant of Rho or Rac, but not Cdc42, prevented gene transactivation and decreased AP-1 activity downstream of Gα<SUB>12</SUB> and Gα<SUB>13</SUB>. In summary, Gα<SUB>12</SUB> and Gα<SUB>13</SUB> regulate the expression of the TGFβ1 gene through an increase in Rho/Rac-dependent AP-1 activity, implying that the G-protein-coupled receptor (GPCR)-Gα<SUB>12</SUB> pathway is involved in the TGFβ1-mediated transdifferentiation process.Oncogene (2009) 28, 1230–1240; doi:10.1038/onc.2008.488; published online 19 January 2009

Full-length genomic analysis of porcine G9P[23] and G9P[7] rotavirus strains isolated from pigs with diarrhea in South Korea

Kim, H.H.,Matthijnssens, J.,Kim, H.J.,Kwon, H.J.,Park, J.G.,Son, K.Y.,Ryu, E.H.,Kim, D.S.,Lee, W.S.,Kang, M.I.,Yang, D.K.,Hyun, B.H.,Park, S.I.,Park, S.J.,Cho, K.O. Elsevier Science 2012 INFECTION GENETICS AND EVOLUTION Vol.12 No.7

Group A rotaviruses (RVAs) are agents causing severe gastroenteritis in infants and young animals. G9 RVA strains are believed to have originated from pigs. However, this genotype has emerged as the fifth major human RVA genotype worldwide. To better understand the relationship between human and porcine RVA strains, complete RVA genome data are needed. For human RVA strains, the number of complete genome data have grown exponentially. However, there is still a lack of complete genome data on porcine RVA strains. Recently, G9 RVA strains have been identified as the third most important genotype in diarrheic pigs in South Korea in combinations with P[7] and P[23]. This study is the first report on complete genome analyses of 1 G9P[7] and 3 G9P[23] porcine RVA strains, resulting in the following genotype constellation: G9-P[7]/P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1. By comparisons of these genotype constellations, it was revealed that the Korean G9P[7] and G9P[23] RVA strains possessed a typical porcine RVA backbone, similar to other known porcine RVA strains. However, detailed phylogenetic analyses revealed the presence of intra-genotype reassortments among porcine RVA strains in South Korea. Thus, our data provide genetic information of G9 RVA strains increasingly detected in both humans and pigs, and will help to establish the role of pigs as a source or reservoir for novel human RVA strains.

Effect of the Transformed Lactobacillus with Phytase Gene on Pig Production Performance, Nutrient Digestibility, Gut Microbes and Serum Biochemical Indexes

Yin, Q.Q.,Chang, J.,Zuo, R.Y.,Chen, L.Y.,Chen, Q.X.,Wei, X.Y.,Guan, Q.F.,Sun, J.W.,Zheng, Q.H.,Yang, X.,Ren, G.Z. Asian Australasian Association of Animal Productio 2010 Animal Bioscience Vol.23 No.2

In order to improve the availability of phytase and probiotics together, a phytase gene from Aspergillus ficuum has been expressed in Lactobacillus. In this study, the transformed Lactobacillus with phytase gene was fed to pigs to determine its effect on pig production, feed conversion and gut microbes. Forty eight, 60-day-old, castrated pigs (Duroc${\times}$Landrace${\times}$Pietrain) were assigned to 6 groups, 8 pigs for each group. Group 1 was the control, group 2 was added with chlortetracycline (500 mg/kg), group 3 was added with the transformed Lactobacillus (500 mg/kg) with 20% (w/w) of calcium monohydrogen phosphate (CMP, $CaHPO_{4}$) removed, group 4 was added with the natural Lactobacillus (500 mg/kg) with 20% (w/w) of CMP removed, group 5 was added with the transformed Lactobacillus (500 mg/kg) with 40% (w/w) of CMP removed, group 6 was added with phytase (500 mg/kg) with 40% (w/w) of CMP removed. The results showed: i) the average daily gain (ADG) was improved in groups 2, 3 and 4 (p<0.05); ii) the diarrhea rates in the groups added with Lactobacillus were lower than in the other groups (p<0.05), in which the transformed Lactobacillus had more effect on reducing digestive disease; iii) the transformed Lactobacillus was most effective in improving the digestibilities of crude protein (CP), calcium (Ca), phosphorus (P), compared with the other groups (p<0.05); iv) Lactobacillus could increase lactic acid bacterium number and ammonia concentrations, and decrease pH values and E. coli number in pig feces (p<0.05); v) the phytase activity in the feces of pigs fed with the transformed Lactobacillus was 133.32 U/g, which was higher than in group 4 (9.58 U/g, p<0.05), and was almost the same as group 6 (135.94 U/g); vi) the transformed Lactobacillus could increase serum concentrations of IgA, triglyceride, and glutamic oxaloacetic transaminase activity (p<0.05), and had no significant effect on other serum indexes (p>0.05).

DED 공정을 이용한 SCM440 기저부 위 G6 분말 적층시 기저부 형상에 따른 열-기계 특성 분석

양지완(J. W. Yang),이광규(K. K. Lee),안동규(D. G. Ahn) 한국기계가공학회 2022 한국기계가공학회 춘추계학술대회 논문집 Vol.2022 No.12

우리나라보호지역시스템에 대한관리효과성평가

허학영(Hag Young Heo),M. Hockings,신원우(W. W. Shin),정혁진(H. J. Chung),N. Dudley,P. Shadie,R. Vaisanen,G. Vincent,김현(H. Kim),박소영(S. Y. Park),양성우(S. W. Yang) 국립공원연구원 2010 국립공원연구지 Vol.1 No.3

생물다양성협약(CBD) 제7차 당사국총회에서 채택된 보호지역실행프로그램(PoWPA)은 당사국들에게 그들의 보호지역에 대한 관리효과성 평가 수행을 권고하고 있다. 이 연구의 목적은 생물다양성협약의 권고사항 이행과 더불어 한국 보호지역시스템에 대한 진단 및 관리 개선을 위한 권고사항을 도출하고자 하였다. 평가 대상지는 환경부에서 관할하고 있는 국립공원, 생태경관보전지역, 습지보호지역, 야생동식물특별보호지역 총 39개소(6,898 km2)를 대상으로 하였다. 평가는 2가지 차원에서 수행되었는데 39개 보호지역(한국 보호지역의 면적 대비 40%정도)에 대한 개별 평가와 한국보호지역시스템에 대한 평가가 이뤄졌으며, 시스템 평가는 국제전문가들과 함께 현장조사, 관리자 및 이해관계자인터뷰, 문헌검토 등을 통해 수행되었다. 평가 결과 개별 보호지역이 국제적으로 잘 관리되고 있었으며, 거버넌스와 행정부분이 다른 나라에 비해 상대적으로 강점으로 나타났고, 생물다양성보호와 자연자연관리에 대한 조화와 협력 부분이 상대적으로 미흡한 것으로 나타났다. 또한 비전과 계획 부분이 특히 강하며, 전반적인 국민의 높은 지지가 매우 인상적이지만, 다른 여러 나라들과 마찬가지로 지역사회협력 부분이 약한 것으로 나타났다. 보호지역의 관리를 개선하기 위한 10가지 주요 권고사항은 보전을 위한 지역적 접근 강화, 보호지역시스템계획 강화, 기관간 통합적 관리 개선, 지역사회와 협력 개선, 이해관계자와 협력 강화, 지방정부와의 협력 개선, 인력관리 재고, 재원 다양화, 연구과제 다양화, 자연자원과 문화자원의 관리 조화 개선 등이다. The Convention on Biological Diversity (CBD)’s Programme of Work on Protected Areas (PoWPA), which was adopted in CoP-7 in 2004, calls on countries to undertake assessments of the effectiveness of management of their protected areas (PA). The objectives of this study are to implement a recommendation of PoWPA, to review the current management status of PA system, and to find out some recommendations for the better management of protected areas in Korea. Assessment Sites are 39 protected areas (6,898 km2) managed under Ministry of Environment which are National parks, Ecosystem & landscape conservation areas, Wetland protected areas, and Wildlife special protected areas. The assessment was conducted at two levels: a site assessment of 39 protected areas, representing about 40% by area of the Korean PA system and a system-level assessment conducted by an international review team incorporating field visits, interviews with staff and stakeholders and review of relevant documentation. The assessment results generally show that individual protected areas are well managed on any international comparison. Governance and administration appears to be relatively stronger in Korea than in other countries, however harmonization and coordination of biodiversity protection and natural resource management remains relatively weaker. Korea also appears to be particularly strong in vision and planning. Korea’s trend toward increasingly high levels of overall public approval is globally impressive; however, as is the case in the rest of the world, community engagement at local levels remains weak and problematic. Ten key recommendations for improving management were to develop a more regional approach to conservation, strengthen PA system planning, better integrate management across agencies within Korea, improve local community relations, enhance interaction with stakeholders, improve integration with regional government, review staff management practices, diversify the funding base, broaden the focus of internal research work and better harmonize natural and cultural resource management.

제주도의 도로특성에 따른 전기자동차의 주행성능 평가

양원호(W. H. Yang),김홍석(H. S. Kim),현명택(M. T. Hyun),김귀식(G. S. Kim) 한국동력기계공학회 2005 한국동력기계공학회 학술대회 논문집 Vol.- No.-

Air pollution from auto-vehicle exhausted gas accounts for 70% of entire air pollution in Jeju. The introduction of electric vehicles which do not generate discharge emissions will improve the clean image in Jeju and boost tour industry. Driving tests have been conducted on the 5-16 and Ilju Roads to investigate the driving characteristics of electric vehicles, using Santa Fes provided by HyunDai Motor Co. The state of charging battery decreases rapidly on the uphill road of 5-16 Road, while it shows linear decreases on the flat road of Ilju Road. It is required to improve the charging ability of battery to adopt the electrical vehicle in Jeju.

항공기용 가스터빈 연소기의 수치해석 연구

양시원(S.W. Yang),정승채(S.C. Jung),김신현(S.H. Kim),박희호(H.H. Park),류시양(S.Y. Ryu),유경원(G.W. Ryu) 한국전산유체공학회 2015 한국전산유체공학회 학술대회논문집 Vol.2015 No.5

펨토초 레이저 드릴가공을 위한 고주파 진동구조물의 개발

김건우(G.W. Kim),강봉철(B.C. Kang),조성학(S.H. Cho),박종권(J.K. Park),양민양(M.Y. Yang) 한국생산제조학회 2010 한국공작기계학회 춘계학술대회논문집 Vol.2010 No.-

Introduction of virtual open chamber for testing a weather modification technique in Korea

J-W Cha,K-H Chang,M-J Lee,J-Y Jeong,J-W Jung,H-Y Yang,K-L Kim,Y-C Kim,C-H Kim,K-H Nam,M-K Suk,C-K Jung,H-Y Go,J-H Chae,G-W Lee,Y-H Cho,S-H Jung,H-M Park,Y-A Oh,J-Y Jung,B-G Kim,Y-J Kim,M-H Choi,S-D Ki 한국기상학회 2009 한국기상학회 학술대회 논문집 Vol.2009 No.4