• 생명과학회지
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• 제29권6호
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• pp.645-652
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• 2019

전세계적으로 폐암 발병율은 서서히 감소하는 추세이지만, 여전히 암 관련 사망의 주요 원인으로 지목되고 있으며, 이에 따라 폐암 진단과 치료를 위한 새로운 분자적 지표를 발굴하는 연구가 활발히 이루어지고 있다. 본 연구진이 수행한 기존 연구에 따르면 폐암 환자에게서는 전사인자 중 하나인 TFAP2C가 높은 비율로 발현되며, 이 전사인자를 통해 폐암 발달에 상당한 영향을 끼치는 것을 확인할 수 있었다. TFAP2C는 다른 유전자들의 발현을 조절하여 암 형성에 기여하게 된다. 마이크로어레이 분석을 통해 TFAP2C에 의해 발현양이 조절되는 잠재적 표적 유전자들을 확인하였고, 특히 TFAP2C siRNA를 처리하였을 때 발현이 감소되는 원암유전자들 중 CDC20과 TRIB3 유전자를 최종적으로 선별하였다. 리얼타임 qRT-PCR과 웨스턴블롯을 통하여 두 유전자가 TFAP2C에 의존적으로 발현됨을 확인하였으며, 세포 생존 분석법을 통하여 CDC20과 TRIB3의 발현 증가가 폐암세포의 세포 증식을 유의미하게 유도하는 것을 확인하였다. 이와 더불어, CDC20과 TRIB3의 과발현이 폐암세포의 세포사멸 수준을 감소시켜 폐암 형성에 관여함을 확인하였다. 본 연구를 통하여 CDC20과 TRIB3가 폐암 형성을 유도할 수 있는 잠재적인 원암유전자로 기능함을 밝힐 수 있었으며, 두 유전자가 폐암 진단을 위한 표적유전자로서의 역할을 수행할 수 있을 것으로 기대한다.

• Molecules and Cells
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• 제42권6호
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• pp.448-459
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• 2019

The phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway is a promising target for gastric cancer (GC) treatment; however the efficacy of PI3K/mTOR dual inhibitors in GC has not yet been maximized. Additionally, the effect of autophagy regulation by PI3K/mTOR dual inhibitors has not been clearly elucidated in GC treatment. We aimed to show that our newly developed PI3K/mTOR dual inhibitor, CMG002, when combined with an autophagy inhibitor, chloroquine (CQ), potently induces effective cancer cell death in Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) cells, where both the PI3K/AKT/mTOR and autophagy pathways play important roles in disease pathogenesis. EBV- and mock-infected AGS and NUGC3 GC cell lines were treated with CMG002 +/- CQ. PI3K/AKT/mTOR signaling pathway mediators, cellular apoptosis and autophagy markers were confirmed by Western blot assay. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. CMG002 effectively blocked the PI3K/AKT/mTOR pathway by markedly decreasing phosphorylation of AKT and its downstream mediator S6. CMG002 induced G0/G1 cell cycle arrest and enhanced apoptotic cell death in AGS and NUGC3 cells, particularly EBV-infected cells compared with mock-infected cells, as confirmed by flow cytometric analyses and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays. The combination of CMG002 plus CQ synergistically increased apoptotic cell death in EBV-infected GC cell lines when compared with CMG002 alone (P < 0.05). Our results suggest that the new PI3K/mTOR dual inhibitor, CMG002, when used in combination with the autophagy inhibitor, CQ, provides enhanced therapeutic efficacy against EBVaGC.

• Yonsei Medical Journal
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• 제59권9호
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• pp.1072-1078
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• 2018

Purpose: The Korean society has moved rapidly toward becoming a multicultural society. This study aimed to estimate the seroprevalence of hepatitis viruses and investigate hepatitis B virus (HBV) genotypic diversity in female marriage immigrants. Materials and Methods: Screening program was conducted at support centers for multicultural families in 21 administrative districts in Korea between July 2011 and January 2017. A total of 963 female marriage immigrants were included in this study. Blood samples were tested for hepatitis viral markers and HBV genotype. Results: Subjects' median age was 33 years (20-40 years), and they originated from nine countries including Vietnam (n=422, 43.8%), China (n=311, 32.3%), the Philippines (n=85, 8.8%), Cambodia (n=58, 6.0%), and Japan (n=39, 4.0%). About 30% (n=288) of subjects required hepatitis A vaccination. HBsAg positive rate was 5.4% (n=52). Positive HBsAg results were the highest in subjects from Southeast Asia (6.6%, n=38). Anti-HBs positive rate was 60.4% (n=582). About 34% (n=329) of subjects who were negative for anti-HBs and HBsAg required HBV vaccinations. Genotypes B and C were found in 54.6% (n=12) and 45.4% (n=10) of the 22 subjects with HBV, in whom genotypes were tested. Eight (0.8%) subjects were positive for anti-HCV. Positive anti-HCV results were the highest in subjects from Central Asia (7.9%, n=3). Conclusion: Testing for hepatitis viral marker (hepatitis A virus IgG and HBsAg/anti-HBs) is needed for female marriage immigrants. Especially, HBV genotype B is different from genotype C of Koreans. Therefore, interest and attention to vaccination programs for female marriage immigrants are necessary for both clinicians and public health institutes.

• Plant Breeding and Biotechnology
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• 제5권3호
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• pp.243-251
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• 2017

Rhus chinensis is a shrub widely distributed in Asia. It has been used for traditional medicine and ecological restoration. Here, we report the complete chloroplast genome sequence of two R. chinensis genotypes collected from China and Korea. The assembled chloroplast genome of Chinese R. chinensis is 149,094 bp long, consisting of a large single copy (97,246 bp), a small single copy (18,644 bp) and a pair of inverted repeats (16,602 bp). Gene annotation revealed 77 protein coding genes, 30 tRNA genes, and 4 rRNA genes. A phylogenomic analysis of the chloroplast genomes with 11 known complete chloroplast genomes clarified the relationship of R. chinensis with the other plant species in the Sapindales order. A comparative chloroplast genome analysis identified 170 SNPs and 85 InDels at intra-species level of R. chinensis between Chinese and Korean collections. Based on the sequence diversity between Korea and Chinese R. chinensis plants, we developed three DNA markers useful for genetic diversity and authentication system. The chloroplast genome information obtained in this study will contribute to enriching genetic resources and conservation of endemic Rhus species.

• Animal Bioscience
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• 제34권7호
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• pp.1105-1115
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• 2021

Objective: To conserve and utilize the genetic resources of a traditional Chinese indigenous pig breed, Liangshan pig, we assessed the genetic diversity, genetic structure, and genetic distance in this study. Methods: We used 50K single nucleotide polymorphism (SNP) chip for SNP detection of 139 individuals in the Liangshan Pig Conservation Farm. Results: The genetically closed conserved population consisted of five overlapping generations, and the total effective content of the population (Ne) was 15. The whole population was divided into five boar families and one non-boar family. Among them, the effective size of each generation subpopulation continuously decreased. However, the proportion of polymorphic markers (P_N) first decreased and then increased. The average genetic distance of these 139 Liangshan pigs was 0.2823±0.0259, and the average genetic distance of the 14 boars was 0.2723±0.0384. Thus, it can be deduced that the genetic distance changed from generation to generation. In the conserved population, 983 runs of homozygosity (ROH) were detected, and the majority of ROH (80%) were within 100 Mb. The inbreeding coefficient calculated based on ROH showed an average value of 0.026 for the whole population. In addition, the inbreeding coefficient of each generation subpopulation initially increased and then decreased. In the pedigree of the whole conserved population, the error rate of paternal information was more than 11.35% while the maternal information was more than 2.13%. Conclusion: This molecular study of the population genetic structure of Liangshan pig showed loss of genetic diversity during the closed cross-generation reproduction process. It is necessary to improve the mating plan or introduce new outside blood to ensure long-term preservation of Liangshan pig.

• Journal of Ginseng Research
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• 제45권3호
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• pp.433-441
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• 2021

Background: Multiple sclerosis (MS) and its animal model, the experimental autoimmune encephalomyelitis (EAE), are primarily characterized as dysfunction of the blood-brain barrier (BBB). Ginsenoside-Rg3-enriched Korean Red Ginseng extract (Rg3-KRGE) is known to exert neuroprotective, anti-inflammatory, and anti-oxidative effects on neurological disorders. However, effects of Rg3-KRGE in EAE remain unclear. Methods: Here, we investigated whether Rg3-KRGE may improve the symptoms and pathological features of myelin oligodendroglial glycoprotein (MOG)_35-55 peptide - induced chronic EAE mice through improving the integrity of the BBB. Results: Rg3-KRGE decreased EAE score and spinal demyelination. Rg3-KRGE inhibited Evan's blue dye leakage in spinal cord, suppressed increases of adhesion molecule platelet endothelial cell adhesion molecule-1, extracellular matrix proteins fibronection, and matrix metallopeptidase-9, and prevented decreases of tight junction proteins zonula occludens-1, claudin-3, and claudin-5 in spinal cord following EAE induction. Rg3-KRGE repressed increases of proinflammatory transcripts cyclooxygenase-2, inducible nitric oxide synthase, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor-alpha, but enhanced expression levels of anti-inflammatory transcripts arginase-1 and IL-10 in the spinal cord following EAE induction. Rg3-KRGE inhibited the expression of oxidative stress markers (MitoSOX and 4-hydroxynonenal), the enhancement of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and NOX4, and NADPH activity in the spinal cord of chronic EAE mice. Furthermore, apocynin, a NOX inhibitor, mimicked beneficial effects of Rg3-KRGE in chronic EAE mice. Conclusion: Our findings suggest that Rg3-KRGE might alleviate behavioral symptoms and pathological features of MS by improving BBB integrity through modulation of NOX2/4 expression.

• 한국식품위생안전성학회지
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• 제35권6호
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• pp.535-543
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• 2020

유전적 조절, 유전자 발현 그리고 환경적 단서, 화학적 신호에 대응하는 표현형 변이에서 세포 RNA는 ubiquitous 역할 이외에도 세포 외 RNA(exRNA)라 하는 새로운 형태의 RNA는 추후 연구의 방향을 제시한다. exRNA는 membrane vesicles 또는 세포 외 소포체(EV)로 알려진 membrane blebs를 통해 세포 외부로 운반된다. EV의 형성은 원핵생물, 진핵생물, 고세균을 포함한 모든 미생물군에 우세하게 보존되어있다. 본 리뷰는 세균 유래 exRNA에 관해 세가지 주제에 초점을 두었다. exRNA의 발견과 박테리아 유전자 배열에 대한 외부 RNA의 영향, b. exRNA의 분비기작을 통한 방출, c. 다른 그람음성 및 그람양성균에 의해 분비되는 exRNA로 고안될 수 있는 응용 가능분야이다. 본 리뷰에서 장내 미생물군의 probiotics 및 후성유전학적 규제에서 본 exRNA와 exRNA마커와 같은 EV파생 응용프로그램에 대한 의견을 제공할 것이다.

• BMB Reports
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• 제55권2호
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• pp.87-91
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• 2022

Aurora kinase is a family of serine/threonine kinases intimately associated with mitotic progression and the development of human cancers. Studies have shown that aurora kinases are important for the protein kinase C (PKC)-induced invasion of colon cancer cells. Recent studies have shown that aurora kinase A promotes distant metastasis by inducing epithelial-to-mesenchymal transition (EMT) in colon cancer cells. However, the role of aurora kinase A in colon cancer metastasis remains unclear. In this study, we investigated the effects of aurora kinase A on PKC-induced cell invasion, migration, and EMT in human SW480 colon cancer cells. Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) changed the expression levels of EMT markers, increasing α-SMA, vimentin, and MMP-9 expression and decreasing E-cadherin expression, with changes in cell morphology. TPA treatment induced EMT in a PKC-dependent manner. Moreover, the inhibition of aurora kinase A by siRNAs and inhibitors (reversine and VX-680) suppressed TPA-induced cell invasion, migration, and EMT in SW480 human colon cells. Inhibition of aurora kinase A blocked TPA-induced vimentin and MMP-9 expression, and decreased E-cadherin expression. Furthermore, the knockdown of aurora kinase A decreased the transcriptional activity of NF-κB and AP-1 in PKC-stimulated SW480 cells. These findings indicate that aurora kinase A induces migration and invasion by inducing EMT in SW480 colon cancer cells. To the best of our knowledge, this is the first study that showed aurora kinase A is a key molecule in PKC-induced metastasis in colon cancer cells.

• BMB Reports
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• 제55권2호
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• pp.81-86
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• 2022

Macrophages are a major cellular component of innate immunity and are mainly known to have phagocytic activity. In the tumor microenvironment (TME), they can be differentiated into tumor-associated macrophages (TAMs). As the most abundant immune cells in the TME, TAMs promote tumor progression by enhancing angiogenesis, suppressing T cells and increasing immunosuppressive cytokine production. N-myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor gene, whose expression is down-regulated in various cancers. However, the effect of NDRG2 on the differentiation of macrophages into TAMs in breast cancer remains elusive. In this study, we investigated the effect of NDRG2 expression in breast cancer cells on the differentiation of macrophages into TAMs. Compared to tumor cell-conditioned medium (TCCM) from 4T1-mock cells, TCCM from NDRG2-over-expressing 4T1 mouse breast cancer cells did not significantly change the morphology of RAW 264.7 cells. However, TCCM from 4T1-NDRG2 cells reduced the mRNA levels of TAM-related genes, including MR1, IL-10, ARG1 and iNOS, in RAW 264.7 cells. In addition, TCCM from 4T1-NDRG2 cells reduced the expression of TAM-related surface markers, such as CD206, in peritoneal macrophages (PEM). The mRNA expression of TAM-related genes, including IL-10, YM1, FIZZ1, MR1, ARG1 and iNOS, was also downregulated by TCCM from 4T1-NDRG2 cells. Remarkably, TCCM from 4T1-NDRG2 cells reduced the expression of PD-L1 and Fra-1 as well as the production of GM-CSF, IL-10 and ROS, leading to the attenuation of T cell-inhibitory activity of PEM. These data showed that compared with TCCM from 4T1-mock cells, TCCM from 4T1-NDRG2 cells suppressed the TAM differentiation and activation. Collectively, these results suggest that NDRG2 expression in breast cancer may reduce the differentiation of macrophages into TAMs in the TME.

• 생명과학회지
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• 제32권9호
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• pp.690-697
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• 2022

본 연구는 홍해삼의 유전체를 분석하여 홍해삼의 유전자 마커 개발을 위한 기초 자료로 활용하기 위해 수행되었다. 울릉도_일반과 울릉도_토착으로 microsatellite marker 분석을 실시하였다. 그 결과 dinucleotide repeat 서열이 81.3~81.4%로 가장 많이 차지 되었으며, 반복서열 개수가 증가될수록 감소되는 경향을 보였다. 일반적으로 microsatellite는 5~10 반복수 사이에 집중적으로 존재하였으며, 반복 서열의 크기가 클수록 반복수가 적어지는 양상을 보였다. Di, tri, tetra-nucleotides 반복에서 각각 (AT)₅, (AAT)₅, (AAAT)₅ 등이 가장 높은 것들로 나타났다. (CG), (CCG) 등은 동일 반복 단위의 다른 반복 단위에 비교하여 매우 낮게 관찰되었다. Di-와 tri-nucleotide는 반복수가 각각 35와 32까지 지속적으로 나타난 다음에 비연속적으로 44와 43 반복까지 계수 되었다. Tetra-, penta- 및 hexa-nucleotide는 각각 25, 21 및 14까지 연속적으로 나타났다. 본 분석결과에 따르면 microsatellite는 특이서열반복에 대해 편중되는 경향성을 보이는 것으로 나타났다. 따라서 홍해삼의 microsatellite 분석에서 고유의 반복 서열과 반복수를 유지하는 것으로 추정되므로 향후 연구를 위한 기초 자료로 활용하는 것이 가능할 것으로 판단된다.