• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9791-9795
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• 2014

To study the gene expression change and possible signal pathway during androgen-dependent prostate cancer (ADPC) becoming androgen-independent prostate cancer (AIPC), an LNCaP cell model of AIPC was established using flutamide in combination with androgen-free environment inducement, and differential expression genes were screened by microarray. Then the biological process, molecular function and KEGG pathway of differential expression genes are analyzed by Molecule Annotation System (MAS). By comparison of 12,207 expression genes, 347 expression genes were acquired, of which 156 were up-ragulated and 191 down-regulated. After analyzing the biological process and molecule function of differential expression genes, these genes are found to play crucial roles in cell proliferation, differntiation, cell cycle control, protein metabolism and modification and other biological process, serve as signal molecules, enzymes, peptide hormones, cytokines, cytoskeletal proteins and adhesion molecules. The analysis of KEGG show that the relevant genes of AIPC transformation participate in glutathione metabolism, cell cycle, P53 signal pathway, cytochrome P450 metabolism, Hedgehog signal pathway, MAPK signal pathway, adipocytokines signal pathway, PPAR signal pathway, TGF-${\beta}$ signal pathway and JAK-STAT signal pathway. In conclusion, during the process of ADPC becoming AIPC, it is not only one specific gene or pathway, but multiple genes and pathways that change. The findings above lay the foundation for study of AIPC mechanism and development of AIPC targeting drugs.

• 환경생물
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• 제26권4호
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• pp.377-384
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• 2008

A cell is the product of a long period of evolution and can be represented as an optimized system (homeostasis). Stimuli from the outside environment are received by sensory apparatus on the surface of the cell and transferred through complicated pathways and eventually regulate gene expression. These signals affect cell physiology, growth, and development, and the interaction among genes in the signal transduction pathway is a critical part of the regulation. In this study, the interactions of deletion mutants and overexpression of the extracopies of the genes were used to understand their relationships to each other. Also, green fluorescent protein (GFP reporter gene) was fused to the regulatory genes to elucidate their interactions. Cooverexpression of the two genes in extracopy plasmids suggested that patS acts at the downstream of hetR in the regulatory network. The experiments using gfp fusion in different genetic background cells also indicated the epistasis relationships between the two genes. A model describing the regulatory network that controls cell development is presented.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-1
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• pp.60-61
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• 2003

Human Genome Project has recently been completed and the information on nucleotide sequences of our whole genome is now available at the public or commercial data banks. Next goals are to identify the functions of each gene and to elucidate the intracellular signal transduction pathways regulating gene expression. We have established a PCR-based bioassay to search for biologically active compounds that can modulate the expression of genes encoding important proteins. (omitted)

• Mycobiology
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• 제39권4호
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• pp.249-256
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• 2011

Microorganisms are significantly affected when the ambient pH of their environment changes. They must therefore be able to sense and respond to these changes in order to survive. Previous investigators have studied various fungal species to define conserved pH-responsive signaling pathways. One of these pathways, known as the Pal/Rim pathway, is activated in response to alkaline pH signals, ultimately targeting the PacC/Rim101 transcription factor. Although the central signaling components are conserved among divergent filamentous and yeast-like fungi, there is some degree of signaling specificity between fungal species. This specificity exists primarily in the downstream transcriptional targets of this pathway, likely allowing differential adaptation to species-specific environmental niches. In this review, the role of the Pal/Rim pathway in fungal pH response is discussed. Also highlighted are functional differences present in this pathway among human fungal pathogens, differences that allow these specialized microorganisms to survive in the various micro-environments of the infected human host.

• Archives of Plastic Surgery
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• 제33권1호
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• pp.5-12
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• 2006

Protein tyrosine kinase(PTK), protein kinase C(PKC), oxidase, as a mediator, take a significant role in signal transduction pathway of angiogenesis. The authors utilized the inhibitors, targeting the formation of three co-enzyme in signal transduction pathway in order to quantify the suppression of abnormal vascular endothelial cell proliferation induced by DMH, to compare the level suppression in each up-regulated growth factors, CTGF, CYR61, $ITG{\beta}1$, FHL2, and to identify the relationship between abnormal cell proliferation and signal transduction pathway. Five groups were established; Control group, Group of DMH, Group of DMH-mixed Herbimycin, inhibitor of protein tyrosine kinase, Group of DMH-mixed Calphostin C, inhibitor of protein kinase C, Group Of Dmh-Mixed 10U Catalase, Inhibitor Of oxidase. The rise of vascular endothelial cell was compared by MTT assay, and four growth factors were analysed with RT-PCR method, at pre-administration, 4, 8, 12, and 24 hours after administration. In comparison of abnormal proliferation of vascular endothelial cell induced by DMH, suppression was noticed in Herbimycin and Calphostin C group, and Calphostin C group revealed higher suppression effect. Nevertheless, Catalase group did not have any suppression. In manifestation of four growth factors, Herbimycin and Calphostin C group presented similar manifestation with control group, except in $ITG{\beta}$. Catalse group had similar manifestation with DMH group in all four growth factors. Abnormal proliferation of vascular endothelial cell induced by DMH have a direct relationship with PTK and PKC, more specifically to PKC. Oxidase was confirmed not to have any relevance.

• Molecules and Cells
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• 제41권6호
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• pp.532-544
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• 2018

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. In order to investigate a new treatment fot GIST, we hypothesized the effect of miR-374b targeting PTEN gene-mediated PI3K/Akt signal transduction pathway on proliferation and apoptosis of human gastrointestinal stromal tumor (GIST) cells. We obtained GIST tissues and adjacent normal tissues from 143 patients with GIST to measure the levels of miR-374b, PTEN, PI3K, Akt, caspase9, Bax, MMP2, MMP9, ki67, PCNA, P53 and cyclinD1. Finally, cell viability, cell cycle and apoptosis were detected. According to the KFGG analysis of DEGs, PTEN was involved in a variety of signaling pathways and miRs were associated with cancer development. The results showed that MiR-374b was highly expressed, while PTEN was downregulated in the GIST tissues. The levels of miR-374b, PI3K, AKT and PTEN were related to tumor diameter and pathological stage. Additionally, miR-374b increased the mRNA and protein levels of PI3K, Akt, MMP2, MMP9, P53 and cyclinD1, suggesting that miR-374b activates PI3K/Akt signaling pathway in GIST-T1 cells. Moreover, MiR374b promoted cell viability, migration, invasion, and cell cycle entry, and inhibited apoptosis in GIST cells. Taken together, the results indicated that miR-374b promotes viability and inhibits apoptosis of human GIST cells by targeting PTEN gene through the PI3K/Akt signaling pathway. Thus, this study provides a new potential target for GIST treatment.

• BMB Reports
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• 제55권9호
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• pp.447-452
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• 2022

Neurogenic differentiation 1 (NeuroD1) is an essential transcription factor for neuronal differentiation, maturation, and survival, and is associated with inflammation in lipopolysaccharide (LPS)-induced glial cells; however, the concrete mechanisms are still ambiguous. Therefore, we investigated whether NeuroD1-targeting miRNAs affect inflammation and neuronal apoptosis, as well as the underlying mechanism. First, we confirmed that miR-30a-5p and miR-153-3p, which target NeuroD1, reduced NeuroD1 expression in microglia and astrocytes. In LPS-induced microglia, miR-30a-5p and miR-153-3p suppressed pro-inflammatory cytokines, reactive oxygen species, the phosphorylation of c-Jun N-terminal kinase, extracellular-signal-regulated kinase (ERK), and p38, and the expression of cyclooxygenase and inducible nitric oxide synthase (iNOS) via the NF-κB pathway. Moreover, miR-30a-5p and miR-153-3p inhibited the expression of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasomes, NLRP3, cleaved caspase-1, and IL-1β, which are involved in the innate immune response. In LPS-induced astrocytes, miR-30a-5p and miR-153-3p reduced ERK phosphorylation and iNOS expression via the STAT-3 pathway. Notably, miR-30a-5p exerted greater anti-inflammatory effects than miR-153-3p. Together, these results indicate that miR-30a-5p and miR-153-3p inhibit MAPK/NF-κB pathway in microglia as well as ERK/STAT-3 pathway in astrocytes to reduce LPS-induced neuronal apoptosis. This study highlights the importance of NeuroD1 in microglia and astrocytes neuroinflammation and suggests that it can be regulated by miR-30a-5p and miR-153-3p.

• Experimental and Molecular Medicine
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• 제50권11호
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• pp.10.1-10.11
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• 2018

Although early studies suggested that bladder cancer (BCa) is more prevalent in men than in women, muscle-invasive rates are higher in women than in men, suggesting that sex hormones might play important roles in different stages of BCa progression. In this work, we found that estrogen receptor beta ($ER{\beta}$) could increase BCa cell proliferation and invasion via alteration of miR-92a-mediated DAB2IP (DOC-2/DAB2 interacting protein) signals and that blocking miR-92a expression with an inhibitor could partially reverse $ER{\beta}$-enhanced BCa cell growth and invasion. Further mechanism dissection found that $ER{\beta}$ could increase miR-92a expression at the transcriptional level via binding to the estrogen-response-element (ERE) on the 5' promoter region of its host gene C13orf25. The $ER{\beta}$ up-regulated miR-92a could decrease DAB2IP tumor suppressor expression via binding to the miR-92a binding site located on the DAB2IP 3' UTR. Preclinical studies using an in vivo mouse model also confirmed that targeting this newly identified $ER{\beta}$/miR-92a/DAB2IP signal pathway with small molecules could suppress BCa progression. Together, these results might aid in the development of new therapies via targeting of this $ER{\beta}$-mediated signal pathway to better suppress BCa progression.

• 한국동물학회지
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• 제34권2호
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• pp.131-141
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• 1991

TPA나 PDGF를 처리로 인한 Protein Kinase C의 신호전달은 힌산화에 의해 일어난다. 그렇지만, PKC에 의해 인산화 되어지는 targeting protein은 TAP나 PDGF 처리시에는 분자량이 서로 다른 단백질들이 인산화가 되어졌다. TPA처리한 myoblast에서 분자량 20,000의 단백질이 인산화되었다. PDGF처리한 세포에서는 분자량 40,000의 단백질이 인산화된 반면에 TPA처리로 인산화 되었던 분자량 20,000의 단백질은 탈인산화 되었다. 이러한 결과들은 TPA와 PDGF가 신호전달계의 활성에 있어서 다를 뿐만 아니라 그들은 장시간의 처리동안 PKC의 down regulation에 관계되어 짐을 암시한다. 그러나 PDGF는 TPA의 경우에서 보다 빠른 down regulation을 유도하였다. 면역세포 화학적인 연구에서 PKC의 동위효소인 PKC II는 세포질에, PKC III는 세포질과 인에 각각 분포하고 있었다. Myoblast에 있어서 PCK두가지 형태의 동위효소의 발현은 이들 동위효소들이 signal transduction이나 down regulation의 각기 다른 경로에 개입되어 진다는 것을 암시한다.

• 생명과학회지
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• 제22권10호
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• pp.1428-1433
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• 2012

장수 또는 노화에 관한 연구는 여러 가지 유전적 요인과 생리학적 및 환경 요인들의 복잡한 조합에 의해 결정되므로, 이와 관련된 연구는 매우 흥미로운 분야이나 또한 어려운 주제이다. 지난 수십 년 동안 장수 또는 노화에 관여하는 분자 메커니즘을 찾기 위하여 동물 모델을 사용한 유전학적 접근법으로, 특이적 유전자를 결손 시키는 연구는 귀중한 도구임이 입증되었다. 장수에 관한 첫 번째 연구는 꼬마선충의 돌연변이체에서 발견되었으며, 이 선충의 인슐린/인슐린유사 성장인자-1 회로가 장수에 관여함이 밝혀졌다. 인슐린유사 성장인자-1은 인슐린과 유사한 아미노산 서열을 가진 폴리펩타이드로, 세포의 정상적인 성장과 발달에 관여한다. 이 발견 이후 인슐린/인슐린유사 성장인자-1 회로에 관여하는 많은 인자들이 선충과 초파리 연구에서 장수에 관여함이 밝혀졌다. 또한 특이적 유전자를 결손 시킨 생쥐 모델을 이용한 연구에서도 인슐린/인슐린유사 성장인자-1 회로뿐 아니라 성장호르몬/인슐린유사 성장인자 회로도 장수에 관여함이 지난 수십 년 동안의 연구결과로 밝혀졌다. 간 조직 특이적으로 인슐린유사 성장인자-1 유전자를 결손 시킨 생쥐모델을 이용한 최근의 연구 결과에 의하면 인슐린유사 성장인자-1 자체도 장수에 관여함이 최초로 밝혀졌으며, 이는 인슐린유사 성장인자-1 회로가 무척추동물뿐 아니라 척추동물에서도 장수에 관여함을 명백하게 보여주는 결과이다. 장수를 조절하는 분자 메커니즘은 아직 완전하게 설명되지 않지만, 감소되어진 인슐린유사 성장인자-1의 신호가 장수와 노화의 조절에 중요한 역할을 하며, 인슐린유사 성장인자-1 회로에 관여하는 여러 가지 유전자들의 장수에서의 역할을 유전자 조작된 생쥐모델을 이용하여 집중적으로 검토하려 한다.