33 results on '"Kim, Youn-Jae"'
Search Results
2. Inhibition of BMP signaling overcomes acquired resistance to cetuximab in oral squamous cell carcinomas
- Author
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Yin, Jinlong, Jung, Ji-Eun, Choi, Sun Il, Kim, Sung Soo, Oh, Young Taek, Kim, Tae-Hoon, Choi, Eunji, Lee, Sun Joo, Kim, Hana, Kim, Eun Ok, Lee, Yu Sun, Chang, Hee Jin, Park, Joo Yong, Kim, Yeejeong, Yun, Tak, Heo, Kyun, Kim, Youn-Jae, Kim, Hyunggee, Kim, Yun-Hee, Park, Jong Bae, and Choi, Sung Weon
- Published
- 2018
- Full Text
- View/download PDF
3. Integration Pattern of Human Papillomavirus Is a Strong Prognostic Factor for Disease-Free Survival After Radiation Therapy in Cervical Cancer Patients
- Author
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Joo, Jungnam, Shin, Hye-Jin, Park, Boram, Park, Seog-Yun, Yoo, Chong-Woo, Yoon, Kyong-Ah, Kong, Sun-Young, Kim, Youn-Jae, Kim, Sang Soo, and Kim, Joo-Young
- Published
- 2017
- Full Text
- View/download PDF
4. Hemoglobin Subunit Theta 1 Promotes Proliferation by Reducing Reactive Oxygen Species in Lung Adenocarcinoma.
- Author
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Kim, Kyungho, Choi, Eun-Young, Ahn, Hye-Mi, Kim, Dong-Gun, and Kim, Youn-Jae
- Subjects
ADENOCARCINOMA ,LUNG cancer ,IN vitro studies ,DISEASE progression ,HEMOGLOBINS ,IN vivo studies ,ANTIOXIDANTS ,GENE expression ,COMPARATIVE studies ,OXIDATIVE stress ,CELL proliferation ,DESCRIPTIVE statistics ,RESEARCH funding ,REACTIVE oxygen species ,INFLAMMATORY mediators - Abstract
Simple Summary: Lung adenocarcinoma, a leading cause of cancer-related deaths, poses treatment challenges. This study explores the role of HBQ1 in the disease. Elevated HBQ1 expression in adenocarcinoma tissues correlates with poor survival. Functional experiments reveal HBQ1 as an oncogene, promoting cell proliferation, and as an antioxidant, reducing reactive oxygen species levels. In vivo studies support HBQ1's role in tumor growth, suggesting it as a potential therapeutic target. These findings highlight HBQ1's crucial involvement in lung adenocarcinoma progression, proposing its use as a diagnostic marker and therapeutic target. Lung adenocarcinoma is a crucial contributor to cancer-related mortality; however, effective treatments remain challenging. The present study aimed to investigate the role of hemoglobin subunit theta 1 (HBQ1), an α subunit of hemoglobin whose expression has recently been reported in non-erythroid cells, in lung adenocarcinoma. Comparative analysis showed that HBQ1 expression was significantly higher in lung adenocarcinoma tissues compared to normal lung tissues. Moreover, high HBQ1 expression was correlated with unfavorable overall survival and progression-free survival in patients, highlighting its potential as a prognostic marker. Our functional experiments revealed that when overexpressed, HBQ1 acts as an oncogene, enhancing cell proliferation, whereas HBQ1 knockdown inhibits it. Additionally, HBQ1 exhibited antioxidant properties by reducing basal reactive oxygen species levels, playing a crucial role in lung adenocarcinoma progression. These findings emphasize the critical role of HBQ1 in driving tumor growth and progression in lung adenocarcinoma. Our in vivo studies further supported the role of HBQ1 in lung adenocarcinoma. HBQ1 knockdown resulted in the inhibition of lung adenocarcinoma growth, demonstrating the potential of HBQ1 as a therapeutic target. Our findings highlight the importance of HBQ1 in lung adenocarcinoma and suggest its potential as both a diagnostic marker and a molecular target for therapeutic interventions. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
5. Chromatin structure–based prediction of recurrent noncoding mutations in cancer
- Author
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Kim, Kwoneel, Jang, Kiwon, Yang, Woojin, Choi, Eun-Young, Park, Seong-Min, Bae, Mingyun, Kim, Youn-Jae, and Choi, Jung Kyoon
- Published
- 2016
- Full Text
- View/download PDF
6. Engineered Human Antibody with Improved Endothelin Receptor Type A Binding Affinity, Developability, and Serum Persistence Exhibits Excellent Antitumor Potency.
- Author
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Ko, Sanghwan, Ju, Man-Seok, Ahn, Hye-Mi, Na, Jung-Hyun, Ko, Woo Hyung, Jo, Migyeong, Kyung, Munsu, Lim, Chung Su, Ko, Byoung Joon, Lee, Won-Kyu, Kim, Youn-Jae, and Jung, Sang Taek
- Published
- 2023
- Full Text
- View/download PDF
7. DEAD-box RNA helicase DDX23 modulates glioma malignancy via elevating miR-21 biogenesis
- Author
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Yin, Jinlong, Park, Gunwoo, Lee, Jeong Eun, Choi, Eun Young, Park, Ju Young, Kim, Tae-Hoon, Park, Nayun, Jin, Xiong, Jung, Ji-Eun, Shin, Daye, Hong, Jun Hee, Kim, Hyunggee, Yoo, Heon, Lee, Seung-Hoon, Kim, Youn-Jae, Park, Jong Bae, and Kim, Jong Heon
- Published
- 2015
- Full Text
- View/download PDF
8. Characteristics of carbonaceous materials with nanotubes grown by hot-filament plasma-enhanced chemical vapor deposition method
- Author
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Jung, Kyung Ho, Shin, Yong-Seob, Boo, Jin-Hyo, Kim, Youn-Jae, and Hong, Byungyou
- Published
- 2006
- Full Text
- View/download PDF
9. Nongenomic Inhibition of Catecholamine Secretion by 17β-Estradiol in PC12 Cells
- Author
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Kim, Youn-Jae, Hur, Eun-Mi, Park, Tae-Ju, and Kim, Kyong-Tai
- Published
- 2000
10. Modulation of Nogo receptor 1 expression orchestrates myelin-associated infiltration of glioblastoma.
- Author
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Hong, Jun-Hee, Kang, Sangjo, Sa, Jason K, Park, Gunwoo, Oh, Young Taek, Kim, Tae Hoon, Yin, Jinlong, Kim, Sung Soo, D'Angelo, Fulvio, Koo, Harim, You, Yeonhee, Park, Saewhan, Kwon, Hyung Joon, Kim, Chan Il, Ryu, Haseo, Lin, Weiwei, Park, Eun Jung, Kim, Youn-Jae, Park, Myung-Jin, and Kim, Hyunggee
- Subjects
GLIOBLASTOMA multiforme ,METHYLGUANINE ,MYELIN oligodendrocyte glycoprotein ,TREATMENT effectiveness ,GENES ,GENE ontology ,STEM cells ,CANCER cell differentiation ,PROTEIN metabolism ,ANIMAL experimentation ,GLIOMAS ,PROTEOLYTIC enzymes ,BRAIN tumors ,NERVE tissue ,CELL lines ,MICE - Abstract
As the clinical failure of glioblastoma treatment is attributed by multiple components, including myelin-associated infiltration, assessment of the molecular mechanisms underlying such process and identification of the infiltrating cells have been the primary objectives in glioblastoma research. Here, we adopted radiogenomic analysis to screen for functionally relevant genes that orchestrate the process of glioma cell infiltration through myelin and promote glioblastoma aggressiveness. The receptor of the Nogo ligand (NgR1) was selected as the top candidate through Differentially Expressed Genes (DEG) and Gene Ontology (GO) enrichment analysis. Gain and loss of function studies on NgR1 elucidated its underlying molecular importance in suppressing myelin-associated infiltration in vitro and in vivo. The migratory ability of glioblastoma cells on myelin is reversibly modulated by NgR1 during differentiation and dedifferentiation process through deubiquitinating activity of USP1, which inhibits the degradation of ID1 to downregulate NgR1 expression. Furthermore, pimozide, a well-known antipsychotic drug, upregulates NgR1 by post-translational targeting of USP1, which sensitizes glioma stem cells to myelin inhibition and suppresses myelin-associated infiltration in vivo. In primary human glioblastoma, downregulation of NgR1 expression is associated with highly infiltrative characteristics and poor survival. Together, our findings reveal that loss of NgR1 drives myelin-associated infiltration of glioblastoma and suggest that novel therapeutic strategies aimed at reactivating expression of NgR1 will improve the clinical outcome of glioblastoma patients. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
11. Selection on the regulation of sympathetic nervous activity in humans and chimpanzees.
- Author
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Lee, Kang Seon, Chatterjee, Paramita, Choi, Eun-Young, Sung, Min Kyung, Oh, Jaeho, Won, Hyejung, Park, Seong-Min, Kim, Youn-Jae, Yi, Soojin V., and Choi, Jung Kyoon
- Subjects
EUKARYOTES ,BIOINFORMATICS ,ANIMAL models in research ,GENE expression ,POLYMERASE chain reaction - Abstract
Adrenergic α
2 C receptor (ADRA2C) is an inhibitory modulator of the sympathetic nervous system. Knockout mice for this gene show physiological and behavioural alterations that are associated with the fight-or-flight response. There is evidence of positive selection on the regulation of this gene during chicken domestication. Here, we find that the neuronal expression of ADRA2C is lower in human and chimpanzee than in other primates. On the basis of three-dimensional chromatin structure, we identified a cis-regulatory region whose DNA sequences have been significantly accelerated in human and chimpanzee. Active histone modification marks this region in rhesus macaque but not in human and chimpanzee; instead, repressive marks are enriched in various human brain samples. This region contains two neuron-restrictive silencer factor (NRSF) binding motifs, each of which harbours a polymorphism. Our genotyping and analysis of population genome data indicate that at both polymorphic sites, the derived allele has reached fixation in humans and chimpanzees but not in bonobos, whereas only the ancestral allele is present among macaques. Our CRISPR/Cas9 genome editing and reporter assays show that both derived nucleotides repress ADRA2C, most likely by increasing NRSF binding. In addition, we detected signatures of recent positive selection for lower neuronal ADRA2C expression in humans. Our findings indicate that there has been selective pressure for enhanced sympathetic nervous activity in the evolution of humans and chimpanzees. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
12. The LncRNA EPEL Promotes Lung Cancer Cell Proliferation Through E2F Target Activation.
- Author
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Park, Seong-Min, Choi, Eun-Young, Bae, Dong-Hyuck, Sohn, Hyun Ahm, Kim, Seon-Young, and Kim, Youn-Jae
- Subjects
NON-coding RNA ,CANCER cells ,LUNG cancer ,APOPTOSIS ,CELL proliferation - Abstract
Background/Aims: Recent studies have revealed that many long non-coding RNAs (lncRNAs) play oncogenic or tumor-suppressive roles in various cancers. Lung cancer is the leading cause of cancer-related death worldwide, and many lung cancer patients frequently relapse after surgery, even those in the early stages. However, the oncogenic or tumor-suppressive roles and clinical implications of lncRNAs in lung cancer have not been fully elucidated. Methods: The association between an E2F-mediated cell proliferation enhancing lncRNA (EPEL) expression and lung cancer patient survival was accessed using public microarray data with clinical information. Cancer-related phenotypes were analyzed by the siRNA knockdown of EPEL in two lung cancer cell lines. Gene set analysis of gene expression data were performed to identify pathways regulated by EPEL. RNA immunoprecipitation, RT-qPCR, and ChIP assays were performed to explore the functions of selected target genes regulated by EPEL. Results: EPEL, known as LOC90768 and MGC45800, was associated with the relapse and survival of lung cancer patients and promoted lung cancer cell proliferation through the activation of E2F target genes. EPEL knockdown specifically down-regulated the expression of cell cycle-related E2F target genes, including Cyclin B1 (CCNB1), in lung cancer cells but not that of apoptosis- or metabolism-related E2F target genes. EPEL interacted with E2F1 and regulated the expression of the E2F target genes by changing the binding efficiency of E2F1 to the E2F target promoters. Moreover, the expression levels of EPEL and CCNB1 both alone and in combination were robust prognostic markers for lung cancer. Conclusions: Considering its specific effects on cell cycle-related E2F target genes and its significant association with the prognosis of lung cancer patients, we suggest that the transcriptional regulation of EPEL through E2F target genes is potentially a target for the development of novel therapeutic strategies for lung cancer patients. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
13. Correction: Pigment Epithelium-Derived Factor (PEDF) Expression Induced by EGFRvIII Promotes Self-renewal and Tumor Progression of Glioma Stem Cells.
- Author
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Yin, Jinlong, Park, Gunwoo, Kim, Tae Hoon, Hong, Jun Hee, Kim, Youn-Jae, Jin, Xiong, Kang, Sangjo, Jung, Ji-Eun, Kim, Jeong-Yub, Yun, Hyeongsun, Lee, Jeong Eun, Kim, Minkyung, Chung, Junho, Kim, Hyunggee, Nakano, Ichiro, Gwak, Ho-Shin, Yoo, Heon, Yoo, Byong Chul, Kim, Jong Heon, and Hur, Eun-Mi
- Subjects
PIGMENT epithelium-derived factor ,CELL tumors ,CANCER invasiveness - Abstract
Corrections to the article "Pigment Epithelium-Derived Factor (PEDF) Expression Induced by EGFRvIII Promotes Self-renewal and Tumor Progression of Glioma Stem Cells" are presented.
- Published
- 2016
- Full Text
- View/download PDF
14. Pigment Epithelium-Derived Factor (PEDF) Expression Induced by EGFRvIII Promotes Self-renewal and Tumor Progression of Glioma Stem Cells.
- Author
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Yin, Jinlong, Park, Gunwoo, Kim, Tae Hoon, Hong, Jun Hee, Kim, Youn-Jae, Jin, Xiong, Kang, Sangjo, Jung, Ji-Eun, Kim, Jeong-Yub, Yun, Hyeongsun, Lee, Jeong Eun, Kim, Minkyung, Chung, Junho, Kim, Hyunggee, Nakano, Ichiro, Gwak, Ho-Shin, Yoo, Heon, Yoo, Byong Chul, Kim, Jong Heon, and Hur, Eun-Mi
- Subjects
CANCER invasiveness ,PIGMENT epithelium-derived factor ,CANCER cell growth ,CORPUS callosum ,STEM cells ,CELLULAR signal transduction - Abstract
Epidermal growth factor receptor variant III (EGFRvIII) has been associated with glioma stemness, but the direct molecular mechanism linking the two is largely unknown. Here, we show that EGFRvIII induces the expression and secretion of pigment epithelium-derived factor (PEDF) via activation of signal transducer and activator of transcription 3 (STAT3), thereby promoting self-renewal and tumor progression of glioma stem cells (GSCs). Mechanistically, PEDF sustained GSC self-renewal by Notch1 cleavage, and the generated intracellular domain of Notch1 (NICD) induced the expression of Sox2 through interaction with its promoter region. Furthermore, a subpopulation with high levels of PEDF was capable of infiltration along corpus callosum. Inhibition of PEDF diminished GSC self-renewal and increased survival of orthotopic tumor-bearing mice. Together, these data indicate the novel role of PEDF as a key regulator of GSC and suggest clinical implications. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
15. The ubiquitin ligase human TRIM71 regulates let-7 microRNA biogenesis via modulation of Lin28B protein.
- Author
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Lee, Seo Hyun, Cho, Sungchan, Sun Kim, M., Choi, Kwangman, Cho, Jae Youl, Gwak, Ho-Shin, Kim, Youn-Jae, Yoo, Heon, Lee, Seung-Hoon, Park, Jong Bae, and Kim, Jong Heon
- Abstract
Abstract: let-7 microRNA (miRNA) is implicated in various biological processes, and its downregulation essentially linked to human malignancy. Regulation of gene expression of the let-7 family is critically linked to RNA-binding proteins. For instance, Lin28B and its paralog, Lin28A, inhibit the pre-let-7 precursor from being processed to mature miRNA by recruiting terminal uridyltransferase, TUT4, which adds oligomeric U at the 3′ end, suggesting that deregulation of Lin28B, together with Lin28A, may alter various biological processes through modulation of let-7 expression. Here, we showed that the Lin28B protein level is regulated via ubiquitin-mediated proteasomal degradation, and identified the ubiquitin ligase as human TRIM-NHL domain-containing TRIM71. In cells, TRIM71 negatively regulates Lin28B protein stability by catalyzing polyubiquitination. Compared with its paralog, Lin28A, a C-terminal unique ~50 amino acid stretch of Lin28B is essential for TRIM71 interactions and subsequent polyubiquitination. Moreover, the N-terminal RING finger motif of TRIM71 is critical for protein–protein interactions and polyubiquitination of Lin28B, and consequent let-7 expression. Consistent with the let-7 stimulatory role of TRIM71 via Lin28B polyubiquitination, specific knockdown of TRIM71 led to downregulation of let-7 expression. Expression of one of the known let-7 targets, HMGA2, was derepressed after knockdown of TRIM71. We additionally showed that enhanced expression of let-7 is part of a feedback loop that targets TRIM71 3′UTR, which contains two conserved let-7 target sites. Our findings collectively reveal critical aspects of regulatory complexity of let-7 biogenesis at the posttranscriptional level. [Copyright &y& Elsevier]
- Published
- 2014
- Full Text
- View/download PDF
16. GPR87 Promotes Metastasis through the AKT-eNOS-NO Axis in Lung Adenocarcinoma.
- Author
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Ahn, Hye-Mi, Choi, Eun-Young, and Kim, Youn-Jae
- Subjects
LUNG cancer prognosis ,ADENOCARCINOMA ,LUNG cancer ,PROTEIN kinases ,IN vitro studies ,IN vivo studies ,ANIMAL experimentation ,CANCER invasiveness ,CELL receptors ,METASTASIS ,CELLULAR signal transduction ,OXIDOREDUCTASES - Abstract
Simple Summary: Lung adenocarcinoma is one of the leading causes of cancer-related deaths. Even though advanced anticancer drugs are available, prognosis of patients with lung cancer is dismal and there is an urgent need to explore novel oncogenic mechanisms to overcome these therapeutic limitations. GPR87 is upregulated in various cancers, but its biological function has not yet been established in lung cancer. Here, we discovered that GPR87 is upregulated in lung adenocarcinoma and overexpressed GPR87 contributes to poor prognosis in patients with lung adenocarcinoma. We used GPR87-overexpressing and GPR87-silenced lung adonocarcinoma cell lines, along with in vivo studies, to demonstrate that overexpression of GPR87 promoted invasiveness and metastasis of lung adenocarcinoma cells. Our study identified the AKT-eNOS-NO signaling axis to be the mechanism by which GPR87 exerted its oncogenic function. Lung adenocarcinoma is one of the leading causes of cancer-related deaths. Despite the availability of advanced anticancer drugs for lung cancer treatment, the prognosis of patients still remains poor. There is a need to explore novel oncogenic mechanisms to overcome these therapeutic limitations. The functional experiments in vitro and in vivo were performed to evaluate the role of GPR87 expression on lung adenocarcinoma metastasis. The public lung adenocarcinoma dataset was used to determine the clinical relevance of GPR87 expression in patients with lung adenocarcinoma. GPR87 is upregulated in various cancer; however, the biological function of GPR87 has not yet been established in lung adenocarcinoma. In this study, we found that GPR87 expression is upregulated in lung adenocarcinoma and is associated with poor patient prognosis. Additionally, we showed that GPR87 overexpression promotes invasiveness and metastasis of lung adenocarcinoma cells. Furthermore, we demonstrated that AKT-eNOS-NO signaling is a novel downstream pathway of GPR87 in lung adenocarcinoma. Conversely, we confirmed that silencing of GPR87 expression suppressed these phenotypes. Our results reveal the oncogenic function of GPR87 in cancer progression and metastasis through the activation of eNOS as a key mediator. Therefore, we propose that targeting eNOS could be a novel therapeutic strategy to improve the clinical treatment of lung adenocarcinoma. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
17. Phospholipase signalling networks in cancer.
- Author
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Park, Jong Bae, Lee, Chang Sup, Jang, Jin-Hyeok, Ghim, Jaewang, Kim, Youn-Jae, You, Sungyoung, Hwang, Daehee, Suh, Pann-Ghill, and Ryu, Sung Ho
- Subjects
PHOSPHOLIPASES ,LYSOPHOSPHOLIPIDS ,CARCINOGENESIS ,CELL proliferation ,ENZYMES ,CANCER cells - Abstract
Phospholipases (PLC, PLD and PLA) are essential mediators of intracellular and intercellular signalling. They can function as phospholipid-hydrolysing enzymes that can generate many bioactive lipid mediators, such as diacylglycerol, phosphatidic acid, lysophosphatidic acid and arachidonic acid. Lipid mediators generated by phospholipases regulate multiple cellular processes that can promote tumorigenesis, including proliferation, migration, invasion and angiogenesis. Although many individual phospholipases have been extensively studied, how phospholipases regulate diverse cancer-associated cellular processes and the interplay between different phospholipases have yet to be fully elucidated. A thorough understanding of the cancer-associated signalling networks of phospholipases is necessary to determine whether these enzymes can be targeted therapeutically. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
18. PTEN Modulates miR-21 Processing via RNA-Regulatory Protein RNH1.
- Author
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Kim, Youn-Jae, Park, Se-Jeong, Choi, Eun Young, Kim, Sol, Kwak, Hee Jin, Yoo, Byong Chul, Yoo, Heon, Lee, Seung-Hoon, Kim, Daesoo, Park, Jong Bae, and Kim, Jong Heon
- Subjects
- *
CANCER , *CELL proliferation , *METASTASIS , *RNA , *APOPTOSIS , *ORIGIN of life - Abstract
Aberrant miR-21 expression is closely associated with cell proliferation, anti-apoptosis, migration, invasion, and metastasis in various cancers. However, the regulatory mechanism of miR-21 biogenesis is largely unknown. Here, we demonstrated that the tumor suppressor PTEN negatively regulates the expression of oncogenic miR-21 at the post-transcriptional level. Moreover, our results suggest that PTEN plays such a role through the indirect interaction with the Drosha complex. To elucidate how PTEN regulates pri- to pre-miR-21 processing, we attempted to find PTEN-interacting proteins and identified an RNA-regulatory protein, RNH1. Using the sensor to monitor pri-miR-21 processing, we demonstrated that RNH1 is necessary and sufficient for pri-miR-21 processing. Moreover, our results propose that the nuclear localization of RNH1 is important for this function. Further analysis showed that RNH1 directly interacts with the Drosha complex and that PTEN blocks this interaction. Taken together, these results suggest that the PTEN-mediated miR-21 regulation is achieved by inhibiting the interaction between the Drosha complex and RNH1, revealing previously unidentified role of PTEN in the oncogenic miR-21 biogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
19. Fast analysis over a wide band using Chebyshev approximation with Clenshaw-Lord approximation.
- Author
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Jeong, Yi-Ru, Hong, Ic-Pyo, Chun, Heoung-Jae, Park, Yong Bae, Kim, Youn-Jae, and Yook, Jong-Gwan
- Published
- 2014
- Full Text
- View/download PDF
20. Blockade of endothelin receptor A enhances the therapeutic efficacy of gemcitabine in pancreatic cancer cells.
- Author
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Ahn, Hye-Mi, Kim, Dong-Gun, and Kim, Youn-Jae
- Subjects
- *
ENDOTHELIN receptors , *PANCREATIC cancer , *TREATMENT effectiveness , *CANCER cells , *CANCER-related mortality - Abstract
Pancreatic adenocarcinoma is currently one of the leading causes of cancer-related death worldwide. The high rate of mortality in pancreatic cancer patients is due to the inability to detect early-stage disease and the disease being highly refractory to therapy. Gemcitabine has been the standard chemotherapy for advanced pancreatic cancer patients for the last two decades. However, gemcitabine resistance develops within a few weeks of treatment, and the associated mechanism remains poorly understood. Therefore, a novel therapeutic strategy is needed to overcome the limited clinical efficacy of gemcitabine in pancreatic adenocarcinoma. In this study, we demonstrated that ET-1/ETAR axis gene expression was upregulated in pancreatic cancer cells after treatment with gemcitabine. Additionally, ETAR expression was significantly higher in tumor tissues than in normal tissues, and patients with high ETAR expression had a notably worse overall survival rate than those with low ETAR expression. Furthermore, our results revealed that bosentan, an ETAR antagonist, enhanced the growth-inhibiting and proapoptotic effects of gemcitabine on pancreatic cancer cells. Thus, our findings indicate that blockade of the ET-1/ETAR axis signaling pathway promotes the antiproliferative effect of gemcitabine on pancreatic cancer. Therefore, combination of ETAR blockade and gemcitabine serves as an effective therapeutic approach to achieve clinical benefits in pancreatic adenocarcinoma patients. • Gemcitabine promoted ET-1/ETAR axis signaling in pancreatic cancer cells. • ETAR overexpression is correlated with a poor prognosis in pancreatic cancer patients. • ETAR antagonist enhanced the growth-inhibiting effect of gemcitabine on pancreatic cancer cells. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
21. Histone variant H3F3A promotes lung cancer cell migration through intronic regulation.
- Author
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Park, Seong-Min, Choi, Eun-Young, Bae, Mingyun, Kim, Sunshin, Park, Jong Bae, Yoo, Heon, Choi, Jung Kyoon, Kim, Youn-Jae, Lee, Seung-Hoon, and Kim, In-Hoo
- Published
- 2016
- Full Text
- View/download PDF
22. RhoBTB3 Regulates Proliferation and Invasion of Breast Cancer Cells via Col1a1.
- Author
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Kim K and Kim YJ
- Subjects
- Cell Line, Tumor, Cell Movement genetics, Cell Proliferation genetics, Female, Gene Expression Regulation, Neoplastic, Humans, Breast Neoplasms pathology, Collagen Type I, alpha 1 Chain metabolism, MicroRNAs genetics, rho GTP-Binding Proteins metabolism
- Abstract
Breast cancer is the leading cause of cancer-related death in women worldwide, despite medical and technological advancements. The RhoBTB family consists of three isoforms: RhoBTB1, RhoBTB2, and RhoBTB3. RhoBTB1 and RhoBTB2 have been proposed as tumor suppressors in breast cancer. However, the roles of RhoBTB3 proteins are unknown in breast cancer. Bioinformatics analysis, including Oncomine, cBioportal, was used to evaluate the potential functions and prognostic values of RhoBTB3 and Col1a1 in breast cancer. qRT-PCR analysis and immunoblotting assay were performed to investigate relevant expression. Functional experiments including proliferation assay, invasion assay, and flow cytometry assay were conducted to determine the role of RhoBTB3 and Col1a1 in breast cancer cells. RhoBTB3 mRNA levels were significantly up-regulated in breast cancer tissues as compared to in adjacent normal tissues. Moreover, RhoBTB3 expression was found to be associated with Col1a1 expression. Decreasing RhoBTB3 expression may lead to decreases in the proliferative and invasive properties of breast cancer cells. Further, Col1a1 knockdown in breast cancer cells limited the proliferative and invasive ability of cancer cells. Knockdown of RhoBTB3 may exert inhibit the proliferation, migration, and metastasis of breast cancer cells by repressing the expression of Col1a1, providing a novel therapeutic strategy for treating breast cancer.
- Published
- 2022
- Full Text
- View/download PDF
23. GPR87 Promotes Metastasis through the AKT-eNOS-NO Axis in Lung Adenocarcinoma.
- Author
-
Ahn HM, Choi EY, and Kim YJ
- Abstract
Lung adenocarcinoma is one of the leading causes of cancer-related deaths. Despite the availability of advanced anticancer drugs for lung cancer treatment, the prognosis of patients still remains poor. There is a need to explore novel oncogenic mechanisms to overcome these therapeutic limitations. The functional experiments in vitro and in vivo were performed to evaluate the role of GPR87 expression on lung adenocarcinoma metastasis. The public lung adenocarcinoma dataset was used to determine the clinical relevance of GPR87 expression in patients with lung adenocarcinoma. GPR87 is upregulated in various cancer; however, the biological function of GPR87 has not yet been established in lung adenocarcinoma. In this study, we found that GPR87 expression is upregulated in lung adenocarcinoma and is associated with poor patient prognosis. Additionally, we showed that GPR87 overexpression promotes invasiveness and metastasis of lung adenocarcinoma cells. Furthermore, we demonstrated that AKT-eNOS-NO signaling is a novel downstream pathway of GPR87 in lung adenocarcinoma. Conversely, we confirmed that silencing of GPR87 expression suppressed these phenotypes. Our results reveal the oncogenic function of GPR87 in cancer progression and metastasis through the activation of eNOS as a key mediator. Therefore, we propose that targeting eNOS could be a novel therapeutic strategy to improve the clinical treatment of lung adenocarcinoma.
- Published
- 2021
- Full Text
- View/download PDF
24. Modulation of Nogo receptor 1 expression orchestrates myelin-associated infiltration of glioblastoma.
- Author
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Hong JH, Kang S, Sa JK, Park G, Oh YT, Kim TH, Yin J, Kim SS, D'Angelo F, Koo H, You Y, Park S, Kwon HJ, Kim CI, Ryu H, Lin W, Park EJ, Kim YJ, Park MJ, Kim H, Kim MS, Chung S, Park CK, Park SH, Kang YH, Kim JH, Saya H, Nakano I, Gwak HS, Yoo H, Lee J, Hur EM, Shi B, Nam DH, Iavarone A, Lee SH, and Park JB
- Subjects
- Animals, Cell Line, Tumor, Female, Gene Expression Regulation, Neoplastic, Humans, Inhibitor of Differentiation Protein 1 metabolism, Inhibitor of Differentiation Proteins metabolism, Mice, Inbred BALB C, Myelin Sheath pathology, Ubiquitin-Specific Proteases metabolism, Mice, Brain Neoplasms metabolism, Brain Neoplasms pathology, Glioblastoma metabolism, Glioblastoma pathology, Myelin Sheath metabolism, Nogo Receptor 1 metabolism
- Abstract
As the clinical failure of glioblastoma treatment is attributed by multiple components, including myelin-associated infiltration, assessment of the molecular mechanisms underlying such process and identification of the infiltrating cells have been the primary objectives in glioblastoma research. Here, we adopted radiogenomic analysis to screen for functionally relevant genes that orchestrate the process of glioma cell infiltration through myelin and promote glioblastoma aggressiveness. The receptor of the Nogo ligand (NgR1) was selected as the top candidate through Differentially Expressed Genes (DEG) and Gene Ontology (GO) enrichment analysis. Gain and loss of function studies on NgR1 elucidated its underlying molecular importance in suppressing myelin-associated infiltration in vitro and in vivo. The migratory ability of glioblastoma cells on myelin is reversibly modulated by NgR1 during differentiation and dedifferentiation process through deubiquitinating activity of USP1, which inhibits the degradation of ID1 to downregulate NgR1 expression. Furthermore, pimozide, a well-known antipsychotic drug, upregulates NgR1 by post-translational targeting of USP1, which sensitizes glioma stem cells to myelin inhibition and suppresses myelin-associated infiltration in vivo. In primary human glioblastoma, downregulation of NgR1 expression is associated with highly infiltrative characteristics and poor survival. Together, our findings reveal that loss of NgR1 drives myelin-associated infiltration of glioblastoma and suggest that novel therapeutic strategies aimed at reactivating expression of NgR1 will improve the clinical outcome of glioblastoma patients., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2021
- Full Text
- View/download PDF
25. A long-range interactive DNA methylation marker panel for the promoters of HOXA9 and HOXA10 predicts survival in breast cancer patients.
- Author
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Park SM, Choi EY, Bae M, Choi JK, and Kim YJ
- Subjects
- CpG Islands, Epigenesis, Genetic, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Homeobox A10 Proteins, Humans, MCF-7 Cells, Prognosis, Promoter Regions, Genetic, Proportional Hazards Models, Survival Analysis, Breast Neoplasms genetics, DNA Methylation, Homeodomain Proteins genetics
- Abstract
Background: Most DNA cancer methylation markers are based on the transcriptional regulation of the promoter-gene relationship. Recently, the importance of long-range interactions between distal CpGs and target genes has been revealed. Here, we attempted to identify methylation markers for breast cancer that interact with distant genes., Results: We performed integrated analysis using chromatin interactome data, methylome data, transcriptome data, and clinical information for breast cancer from public databases. Using the chromatin interactome and methylome data, we defined CpG-distant target gene relationships. After determining the differences in methylation between tumor and paired normal samples, the survival association, and the correlation between CpG methylation and distant target gene expression, we selected CpG methylation marker candidates. Using Cox proportional hazards models, we combined the selected markers and evaluated the prognostic model. We identified six methylation markers in HOXA9 and HOXA10 promoter regions and their long-range target genes. We experimentally validated the chromatin interactions, methylation status, and transcriptional regulation. A prognostic model showed that the combination of six methylation markers was highly associated with poor survival in independent datasets. According to our multivariate analysis, the prognostic model showed significantly better prognostic ability than other histological and molecular markers., Conclusions: The combination of long-range interacting HOXA9 and HOXA10 promoter CpGs predicted the survival of breast cancer patients, providing a comprehensive and novel approach for discovering new methylation markers.
- Published
- 2017
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26. A Human Antibody That Binds to the Sixth Ig-Like Domain of VCAM-1 Blocks Lung Cancer Cell Migration In Vitro.
- Author
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Kim MR, Jang JH, Park CS, Kim TK, Kim YJ, Chung J, Shim H, Nam IH, Han JM, and Lee S
- Subjects
- Animals, Antibodies, Monoclonal pharmacology, Binding Sites, Cell Line, Tumor, Humans, Mice, Vascular Cell Adhesion Molecule-1 chemistry, Antibodies, Monoclonal immunology, Cell Movement drug effects, Lung Neoplasms metabolism, Vascular Cell Adhesion Molecule-1 immunology
- Abstract
Vascular cell adhesion molecule-1 (VCAM-1) is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung tissue, and high VCAM-1 expression correlated with poor survival in lung cancer patients. VCAM-1 knockdown reduced migration of A549 human lung cancer cells into Matrigel, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6) demonstrated that the VCAM-1-D6 domain was critical for VCAM-1 mediated A549 cell migration into Matrigel. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab), which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed the migration of A549 and NCI-H1299 lung cancer cell lines into Matrigel. Taken together, these results suggest that VCAM-1-D6 is a key domain for regulating VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.
- Published
- 2017
- Full Text
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27. Roles of zinc-fingers and homeoboxes 1 during the proliferation, migration, and invasion of glioblastoma cells.
- Author
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Kwon RJ, Han ME, Kim YJ, Kim YH, Kim JY, Liu L, Heo W, and Oh SO
- Subjects
- Adult, Aged, Biomarkers, Tumor biosynthesis, Cell Line, Tumor, Cell Movement, Disease-Free Survival, Female, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Glioblastoma pathology, Homeodomain Proteins biosynthesis, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasm Invasiveness genetics, Neoplasm Invasiveness pathology, Prognosis, Transcription Factors biosynthesis, Biomarkers, Tumor genetics, Cell Proliferation genetics, Glioblastoma genetics, Homeodomain Proteins genetics, Transcription Factors genetics
- Abstract
Zinc-fingers and homeoboxes 1 (ZHX1) is a nuclear transcription repressor and known to be involved in cell differentiation and tumorigenesis. However, the pathophysiological roles of ZHX1 have not been characterized in glioblastoma. We examined ZHX1 expression in glioblastoma patients' tissues and analyzed overall survival of the patients based on expression level of ZHX1. We also examined the effects of ZHX1 on proliferation and motility of glioblastoma cells. In silico analysis and immunohistochemical studies showed that the messenger RNA and protein expressions of ZHX1 were higher in the tissues of glioblastoma patients than in normal brain tissues, and that its overexpression was associated with reduced survival. In vitro, the downregulation of ZHX1 decreased the proliferation, migration, and invasion of glioblastoma cells, whereas its upregulation had the opposite effects. In addition, we showed ZHX1 could contribute to glioblastoma progression via the regulations of TWIST1 and SNAI2. Taken together, this study demonstrates that ZHX1 plays crucial roles in the progression of glioblastoma, and its findings suggest that ZHX1 be viewed as a potential prognostic maker and therapeutic target of glioblastoma.
- Published
- 2017
- Full Text
- View/download PDF
28. Radiation-induced autophagy contributes to cell death and induces apoptosis partly in malignant glioma cells.
- Author
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Jo GH, Bögler O, Chwae YJ, Yoo H, Lee SH, Park JB, Kim YJ, Kim JH, and Gwak HS
- Abstract
Purpose: Radiation-induced autophagy has been shown to play two different roles, in malignant glioma (MG) cells, cytocidal or cytoprotective. However, neither the role of radiation-induced autophagy for cell death nor the existence of autophagy-induced apoptosis, a well-known cell-death pathway after irradiation, has been verified yet., Materials and Methods: We observed both temporal and dose-dependent response patterns of autophagy and apoptosis to radiation in MG cell lines. Additionally, we investigated the role of autophagy in apoptosis through knockdown of autophagy-related proteins., Results: Autophagic activity measured by staining of acidic vesicle organelles and Western blotting of LC-3 protein increased in proportion to radiation dose from day 1 to 5 after irradiation. Apoptosis measured by annexin-V staining and Western blotting of cleaved poly(ADP-ribose) polymerase demonstrated relatively late appearance 3 days after irradiation that increased for up to 7 days. Blocking of pan-caspase (Z-VAD-FMK) did not affect apoptosis after irradiation, but silencing of Atg5 effectively reduced radiation-induced autophagy, which decreased apoptosis significantly. Inhibition of autophagy in Atg5 knockdown cells was shown to be beneficial for cell survival. Stable transfection of GFP-LC3 cells was observed after irradiation. Annexin-V was localized in cells bearing GFP-LC3 punctuated spots, indicating autophagy in immunofluorescence. Some of these punctuated GFP-LC3 bearing cells formed conglomerated spots and died in final phase., Conclusion: These findings suggest that autophagy appears earlier than apoptosis after irradiation and that a portion of the apoptotic population that appears later is autophagy-dependent. Thus, autophagy is a pathway to cell death after irradiation of MG cells.
- Published
- 2015
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29. CPEB1 modulates differentiation of glioma stem cells via downregulation of HES1 and SIRT1 expression.
- Author
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Yin J, Park G, Lee JE, Park JY, Kim TH, Kim YJ, Lee SH, Yoo H, Kim JH, and Park JB
- Subjects
- Animals, Basic Helix-Loop-Helix Transcription Factors genetics, Brain Neoplasms genetics, Brain Neoplasms metabolism, Brain Neoplasms pathology, Cell Differentiation physiology, Down-Regulation, Female, Glioma genetics, Glioma metabolism, HEK293 Cells, Heterografts, Homeodomain Proteins genetics, Humans, Mice, Mice, Inbred BALB C, Sirtuin 1 genetics, Transcription Factor HES-1, Transcription Factors genetics, Transcription Factors metabolism, Transcription, Genetic, Transfection, mRNA Cleavage and Polyadenylation Factors genetics, mRNA Cleavage and Polyadenylation Factors metabolism, Basic Helix-Loop-Helix Transcription Factors biosynthesis, Glioma pathology, Homeodomain Proteins biosynthesis, Neoplastic Stem Cells pathology, Sirtuin 1 biosynthesis, Transcription Factors biosynthesis, mRNA Cleavage and Polyadenylation Factors biosynthesis
- Abstract
Glioma stemness has been recognized as the most important reason for glioma relapse and drug resistance. Differentiation of glioma stem cells (GSCs) has been implicated as a novel approach to target recurrent glioma. However, the detailed molecular mechanism involved in the differentiation of GSCs has not yet been elucidated. This study identified CPEB1 as the key modulator that induces the differentiation of GSCs at the post-transcriptional level. Gain and loss of function experiments showed that CPEB1 expression reduced sphere formation ability and the expression of stemness markers such as Nestin and Notch. To elucidate the detailed molecular mechanism underlying the action of CPEB1, we investigated the interacting ribonome of the CPEB1 complex using a Ribonomics approach. CPEB1 specifically suppressed the translation of HES1 and SIRT1 by interacting with a cytoplasmic polyadenylation element. The expression profile of CPEB1 negatively correlated with overall survival in glioma patients. Overexpression of CPEB1 decreased the number of GSCs in an orthotopically implanted glioma animal model. These results suggest that CPEB1-mediated translational control is essential for the differentiation of GSCs and provides novel therapeutic concepts for differentiation therapy.
- Published
- 2014
- Full Text
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30. The ubiquitin ligase human TRIM71 regulates let-7 microRNA biogenesis via modulation of Lin28B protein.
- Author
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Lee SH, Cho S, Kim MS, Choi K, Cho JY, Gwak HS, Kim YJ, Yoo H, Lee SH, Park JB, and Kim JH
- Subjects
- 3' Untranslated Regions, Cell Line, Down-Regulation, Gene Expression, HEK293 Cells, HMGA2 Protein genetics, HMGA2 Protein metabolism, Humans, MicroRNAs metabolism, Protein Interaction Domains and Motifs, Proteolysis, RING Finger Domains, RNA-Binding Proteins metabolism, Tripartite Motif Proteins, Ubiquitin genetics, Ubiquitin metabolism, Ubiquitin-Protein Ligases metabolism, MicroRNAs biosynthesis, MicroRNAs genetics, RNA-Binding Proteins genetics, Ubiquitin-Protein Ligases genetics
- Abstract
let-7 microRNA (miRNA) is implicated in various biological processes, and its downregulation essentially linked to human malignancy. Regulation of gene expression of the let-7 family is critically linked to RNA-binding proteins. For instance, Lin28B and its paralog, Lin28A, inhibit the pre-let-7 precursor from being processed to mature miRNA by recruiting terminal uridyltransferase, TUT4, which adds oligomeric U at the 3' end, suggesting that deregulation of Lin28B, together with Lin28A, may alter various biological processes through modulation of let-7 expression. Here, we showed that the Lin28B protein level is regulated via ubiquitin-mediated proteasomal degradation, and identified the ubiquitin ligase as human TRIM-NHL domain-containing TRIM71. In cells, TRIM71 negatively regulates Lin28B protein stability by catalyzing polyubiquitination. Compared with its paralog, Lin28A, a C-terminal unique ~50 amino acid stretch of Lin28B is essential for TRIM71 interactions and subsequent polyubiquitination. Moreover, the N-terminal RING finger motif of TRIM71 is critical for protein-protein interactions and polyubiquitination of Lin28B, and consequent let-7 expression. Consistent with the let-7 stimulatory role of TRIM71 via Lin28B polyubiquitination, specific knockdown of TRIM71 led to downregulation of let-7 expression. Expression of one of the known let-7 targets, HMGA2, was derepressed after knockdown of TRIM71. We additionally showed that enhanced expression of let-7 is part of a feedback loop that targets TRIM71 3'UTR, which contains two conserved let-7 target sites. Our findings collectively reveal critical aspects of regulatory complexity of let-7 biogenesis at the posttranscriptional level., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
31. Silencing of microRNA-21 confers radio-sensitivity through inhibition of the PI3K/AKT pathway and enhancing autophagy in malignant glioma cell lines.
- Author
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Gwak HS, Kim TH, Jo GH, Kim YJ, Kwak HJ, Kim JH, Yin J, Yoo H, Lee SH, and Park JB
- Subjects
- Apoptosis radiation effects, Brain Neoplasms pathology, Cell Line, Tumor parasitology, Cell Survival, Gamma Rays, Gene Silencing, Glioma pathology, Histones genetics, Humans, MicroRNAs metabolism, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction genetics, Signal Transduction radiation effects, Autophagy genetics, Brain Neoplasms genetics, Glioma genetics, MicroRNAs genetics, Radiation Tolerance genetics
- Abstract
Radiation is a core part of therapy for malignant glioma and is often provided following debulking surgery. However, resistance to radiation occurs in most patients, and the underlying molecular mechanisms of radio-resistance are not fully understood. Here, we demonstrated that microRNA 21 (miR-21), a well-known onco-microRNA in malignant glioma, is one of the major players in radio-resistance. Radio-resistance in different malignant glioma cell lines measured by cytotoxic cell survival assay was closely associated with miR-21 expression level. Blocking miR-21 with anti-miR-21 resulted in radio-sensitization of U373 and U87 cells, whereas overexpression of miR-21 lead to a decrease in radio-sensitivity of LN18 and LN428 cells. Anti-miR-21 sustained γ-H2AX DNA foci formation, which is an indicator of double-strand DNA damage, up to 24 hours and suppressed phospho-Akt (ser473) expression after exposure to γ-irradiation. In a cell cycle analysis, a significant increase in the G₂/M phase transition by anti-miR-21 was observed at 48 hours after irradiation. Interestingly, our results showed that anti-miR-21 increased factors associated with autophagosome formation and autophagy activity, which was measured by acid vesicular organelles, LC3 protein expression, and the percentage of GFP-LC3 positive cells. Furthermore, augmented autophagy by anti-miR-21 resulted in an increase in the apoptotic population after irradiation. Our results show that miR-21 is a pivotal molecule for circumventing radiation-induced cell death in malignant glioma cells through the regulation of autophagy and provide a novel phenomenon for the acquisition of radio-resistance.
- Published
- 2012
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32. Human brain endothelial cell-derived COX-2 facilitates extravasation of breast cancer cells across the blood-brain barrier.
- Author
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Lee KY, Kim YJ, Yoo H, Lee SH, Park JB, and Kim HJ
- Subjects
- Biological Transport, Breast Neoplasms pathology, Cell Line, Tumor, Cell Movement, Culture Media, Conditioned pharmacology, Female, Humans, Neoplasm Metastasis, RNA, Small Interfering metabolism, Solubility, Blood-Brain Barrier metabolism, Brain metabolism, Breast Neoplasms metabolism, Cyclooxygenase 2 biosynthesis, Endothelial Cells metabolism, Matrix Metalloproteinase 2 biosynthesis
- Abstract
With improvements in systemic control, metastasis to the brain has been more frequently found in patients with breast cancer. In order to gain access to the brain, breast cancer cells must overcome the blood-brain barrier (BBB), a highly selective filter against cellular and soluble substances. Human brain endothelial cells (HBECs) comprise a major element of the BBB, and breast cancer cells first encounter and pass through them for extravasation. To date, however, the precise role of HBECs in metastasis to the brain is unknown. In this study, we examined how HBECs take part in the extravasation process. In an established in vitro model of the BBB, unexpectedly, the transmigration of breast cancer cells was markedly enhanced in the presence of HBECs than in their absence, suggesting that HBECs facilitate the transmigration of breast cancer cells rather than acting as a barrier against them. We then showed that cyclooxygenase (COX-2) induced from HBECs rather than that from breast cancer cells plays a key role in the transmigration. Moreover, expression of matrix metalloproteinase (MMP-2) mediating the transmigration was induced in HBECs by COX-2 after co-culture with breast cancer cells. Taken together, our results suggest that COX-2 and MMP-2 produced from HBECs facilitate the extravasation of breast cancer cells across the BBB.
- Published
- 2011
33. Toward a functional annotation of the human genome using artificial transcription factors.
- Author
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Lee DK, Park JW, Kim YJ, Kim J, Lee Y, Kim J, and Kim JS
- Subjects
- Antigens, Neoplasm genetics, Antigens, Neoplasm physiology, Cell Line, Computational Biology statistics & numerical data, DNA-Binding Proteins genetics, DNA-Binding Proteins physiology, Gene Expression Profiling methods, Gene Expression Profiling statistics & numerical data, Gene Expression Regulation genetics, Genetic Linkage, Humans, Melanoma genetics, Multigene Family, Oligonucleotide Array Sequence Analysis methods, Oligonucleotide Array Sequence Analysis statistics & numerical data, Recombinant Proteins analysis, Transcription Factors genetics, Zinc Fingers genetics, Computational Biology methods, Genome, Human, Transcription Factors physiology
- Abstract
We have developed a novel, high-throughput approach to collecting randomly perturbed gene-expression profiles from the human genome.A human 293 cell library that stably expresses randomly chosen zinc-finger transcription factors was constructed, and the expression profile of each cell line was obtained using cDNA microarray technology.Gene expression profiles from a total of 132 cell lines were collected and analyzed by (1) a simple clustering method based on expression-profile similarity, and (2) the shortest-path analysis method. These analyses identified a number of gene groups, and further investigation revealed that the genes that were grouped together had close biological relationships. The artificial transcription factor-based random genome perturbation method thus provides a novel functional genomic tool for annotation and classification of genes in the human genome and those of many other organisms.
- Published
- 2003
- Full Text
- View/download PDF
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